What is the recommended approach for celiac disease (CD) screening and management?

Celiac Disease Screening and Management Protocol

IgA tissue transglutaminase antibody (tTG-IgA) is the preferred first-line screening test for celiac disease in patients with symptoms or risk factors, followed by duodenal biopsy for confirmation while the patient remains on a gluten-containing diet. 1

Who to Screen

High-Priority Screening Groups:

• Patients with symptoms of malabsorption (chronic diarrhea, weight loss, steatorrhea, postprandial abdominal pain, bloating) 1
• Patients with unexplained iron deficiency anemia 1
• Patients with unexplained elevations in liver transaminase levels 1
• Patients with premature osteoporosis 1
• First-degree relatives of patients with celiac disease 1

Consider Screening In:

• Patients with irritable bowel syndrome-like symptoms 1
• Patients with type 1 diabetes mellitus 1
• Patients with autoimmune thyroid disease 1
• Patients with unexplained infertility or recurrent fetal loss 1
• Patients with Down syndrome 1
• Patients with selective IgA deficiency 1
• Patients with peripheral neuropathy or cerebellar ataxia 1
• Patients with dermatitis herpetiformis 2

Diagnostic Testing Algorithm

Step 1: Serologic Testing

• First-line test: IgA tissue transglutaminase antibody (tTG-IgA) 1
  • Sensitivity: 90-96%
  • Specificity: >95%
• Important: Perform serologic testing BEFORE starting a gluten-free diet 1

Step 2: Additional Testing Based on Initial Results

• If tTG-IgA is positive → Proceed to duodenal biopsy 1
• If tTG-IgA is negative but high clinical suspicion remains:
  • Check total serum IgA level to rule out IgA deficiency 1
  • If IgA deficient → Use IgG-based testing (IgG-tTG or IgG-DGP) 1
  • Consider HLA-DQ2/DQ8 testing (absence effectively rules out celiac disease) 1

Step 3: Confirmatory Testing

• Gold standard: Upper endoscopy with multiple duodenal biopsies 1
  • Obtain at least 4-6 biopsies from second part of duodenum or beyond 3
  • Look for villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes 3
• Diagnosis requires combination of:
  • Compatible clinical features
  • Positive serology
  • Characteristic histopathology 1

Management Protocol

Primary Treatment

• Strict, lifelong gluten-free diet (GFD) under dietitian guidance 1, 3
  • Exclude wheat, rye, barley (and potentially oats)
  • Target less than 10 mg gluten intake per day 3

Nutritional Considerations

• Monitor for common deficiencies: B vitamins, iron, calcium, vitamin D, zinc, magnesium 3
• Recommend alternative gluten-free grains: buckwheat, amaranth, quinoa, millet, sorghum 3
• Consider supplementation for identified deficiencies 3

Follow-up Protocol

• Serological testing at 6 and 12 months after diagnosis, then yearly 3
• Consider follow-up intestinal biopsy after 1-2 years to confirm mucosal healing 3

Management of Non-responsive Celiac Disease (NRCD)

If symptoms persist despite adherence to GFD for 4-6 weeks:

1. Confirm diagnosis: Review original biopsy, serology, HLA status 3
2. Assess GFD adherence: Dietary review, consider testing for gluten immunogenic peptides 3
3. Investigate alternative causes:
   • Microscopic colitis
   • Small intestinal bacterial overgrowth (SIBO)
   • Exocrine pancreatic insufficiency
   • Lactose or fructose intolerance
   • Thyroid dysfunction 3

Refractory Celiac Disease

If symptoms and villous atrophy persist despite confirmed strict GFD adherence for at least 12 months:

• Consider refractory celiac disease (RCD) 3
• Perform advanced testing (flow cytometry, immunohistochemistry, T-cell receptor rearrangement) 3
• Refer to tertiary center for specialized management 1

Important Pitfalls to Avoid

• Do not start a gluten-free diet before completing diagnostic testing 1
• Do not rely on symptom improvement on a gluten-free diet for diagnosis 1
• Do not use antibodies against native gliadin for primary detection 1
• Do not combine multiple serologic tests in low-risk populations 1
• Do not assume persistent symptoms always indicate poor diet adherence 3

By following this evidence-based protocol for celiac disease screening and management, clinicians can improve early detection rates and optimize patient outcomes through appropriate diagnosis and treatment.