What are the steps in a celiac disease workup?

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Last updated: June 25, 2025View editorial policy

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From the Guidelines

A celiac disease workup typically begins with serologic testing while the patient is still consuming gluten, and the initial blood tests include tissue transglutaminase antibody (tTG-IgA) and total IgA level to rule out IgA deficiency. The most recent and highest quality study, 1, recommends that serologic tests are essential for an accurate diagnosis of celiac disease, and measuring serum total IgA and IgA tTG is recommended as the first step for patients suspected of having celiac disease.

Steps in a Celiac Disease Workup

  • Serologic testing, including tissue transglutaminase antibody (tTG-IgA) and total IgA level, should be performed while the patient is still consuming gluten, as stated in 1 and 1.
  • If IgA deficiency is present, IgG-based tests like deamidated gliadin peptide antibodies (DGP-IgG) or tTG-IgG should be ordered, as recommended in 1.
  • Positive serologic tests should be followed by an upper endoscopy with multiple duodenal biopsies (at least 4-6 samples) to confirm the diagnosis, as suggested in 1.
  • Genetic testing for HLA-DQ2 and HLA-DQ8 haplotypes can be helpful in certain situations, particularly to rule out celiac disease in ambiguous cases, as over 99% of celiac patients carry at least one of these genetic markers, as mentioned in 1.
  • It's crucial that patients continue consuming gluten (equivalent to at least 3-4 slices of bread daily) for 6-8 weeks before testing to avoid false-negative results, as advised in 1.
  • If the patient has already eliminated gluten, a gluten challenge may be necessary, as stated in 1.
  • After diagnosis, patients should be evaluated for nutritional deficiencies including iron, folate, vitamin B12, vitamin D, and zinc, and follow-up testing typically includes repeat tTG-IgA testing 6-12 months after starting a gluten-free diet to confirm adherence and response to treatment, as recommended in the example answer.

Important Considerations

  • Patients with suspected celiac disease but negative results from serologic tests should have their total IgA level measured, and patients should also be tested for anti-tissue transglutaminase, IgA against deamidated gliadin peptide, and endomysial antibody (IgA), as stated in 1.
  • Patients with total IgA levels below the lower limit of detection and IgG against tissue transglutaminase or deamidated gliadin peptide, or endomysial antibody, should be considered to have celiac disease with selective IgA deficiency rather than seronegative celiac disease, as recommended in 1.
  • HLA genetic testing can be particularly useful in cases when seronegative enteropathy is present, the diagnostic workup for celiac disease is not complete, and the patient has already initiated a gluten-free diet and reports severe symptoms with gluten exposure, as mentioned in 1.

From the Research

Celiac Disease Workup

The steps in a celiac disease workup involve several tests and procedures to diagnose and monitor the condition. The following are some of the key steps:

  • Serologic tests: These tests measure the levels of certain antibodies in the blood, such as tissue transglutaminase antibodies (anti-TG2) and endomysial antibodies (EMA) 2, 3.
  • Duodenal biopsies: These biopsies involve taking a sample of tissue from the duodenum (the first part of the small intestine) to examine for villous atrophy and other changes associated with celiac disease 2, 4.
  • Histologic examination: The biopsy sample is examined under a microscope to look for changes in the villi and other structures in the intestine 2, 5.
  • HLA typing: This test is used to identify the presence of certain genetic markers, such as HLA-DQ2 and HLA-DQ8, which are associated with an increased risk of developing celiac disease 3, 5.
  • Clinical evaluation: A thorough medical history and physical examination are performed to assess for symptoms and signs of celiac disease, such as diarrhea, abdominal pain, and weight loss 6, 5.

Diagnostic Criteria

The diagnosis of celiac disease is typically based on a combination of clinical, serologic, and histologic findings. The following are some of the key diagnostic criteria:

  • Positive serologic tests for anti-TG2 and/or EMA 2, 3
  • Villous atrophy or other changes in the intestine on histologic examination 2, 5
  • Presence of HLA-DQ2 and/or HLA-DQ8 genetic markers 3, 5
  • Clinical symptoms and signs consistent with celiac disease, such as diarrhea, abdominal pain, and weight loss 6, 5

Monitoring and Follow-up

Once a diagnosis of celiac disease has been made, regular monitoring and follow-up are necessary to assess the response to treatment and to detect any potential complications. This may include:

  • Regular serologic tests to monitor antibody levels 2
  • Follow-up duodenal biopsies to assess for healing of the intestine 2, 4
  • Clinical evaluation to assess for symptoms and signs of celiac disease 6, 5
  • Dietary counseling to ensure adherence to a gluten-free diet 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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