CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Celiac Disease Testing

Criteria for laboratory, genetic, and biopsy testing for diagnosis and confirmation of celiac disease for Blue Cross Blue Shield - Tennessee members; covers which tests meet or do not meet coverage criteria and applicable indications.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyCeliac Disease Testing

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionOrder IgA anti-TTG with total IgA as the preferred initial test and document signs/symptoms or risk status when requesting testing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

About 2MAmericans with celiac disease (est.)

~1%Worldwide prevalence

90–95%HLA‑DQ2 in CD patients

25–40%HLA‑DQ2 prevalence (general pop)

>=10×tTG threshold for pediatric no‑biopsy

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

FDA-approved nucleic acid tests (as of Jul 2019)

Coverage Criteria for Celiac Disease Testing

Medically Necessary / Covered Testing

Covered when specified clinical indications or risk categories are present

Initial serologic testing: For individuals with signs and symptoms of celiac disease, serologic testing with IgA anti-tissue transglutaminase (TTG) AND total IgA meets coverage criteria (perform while on a gluten-containing diet)

See Note 1 for signs and symptoms

Follow-up serologic testing: For at-risk individuals when IgA anti-TTG is negative or weakly positive, testing for IgA endomysial antibodies (EMA-IgA) meets coverage criteria

Testing in IgA deficiency: For individuals with clinical suspicion and IgA deficiency, testing for IgG endomysial antibodies OR IgG deamidated gliadin peptide (DGP) OR IgG TTG meets coverage criteria

Pediatric DGP use: For children under 2 years with clinical suspicion, and for those over 2 years when substituting for anti-TTG testing, IgA and IgG DGP testing meets coverage criteria

HLA genotyping: Genetic testing for HLA DQ2 and DQ8 meets coverage criteria for (a) symptomatic individuals for whom other testing is undiagnostic OR (b) symptomatic individuals with positive serology who are unable to undergo biopsy evaluation

Biopsy confirmation: Biopsy of the small intestine (upper endoscopy with multiple duodenal biopsies) meets coverage criteria for confirmation of celiac disease in individuals at high risk regardless of serology result

Not Covered

Tests explicitly not covered

Point-of-care rapid anti-TTG: Rapid antigen point-of-care testing for anti-TTG does not meet coverage criteria

Panel/multiplex tests: Panel testing, multiplex, or multi-analyte testing for more than two analytes for diagnosis or evaluation of celiac disease does not meet coverage criteria

Anti-reticulin: Testing for anti-reticulin antibodies does not meet coverage criteria

Stool or saliva testing: Testing of stool or saliva samples for evaluation of celiac disease does not meet coverage criteria

HLA-DQ-gluten tetramer assays:

Diagnostic and monitoring criteria

Covered when testing follows specialty society diagnostic algorithms and documentation supports clinical indications

Initial serologic testing: Perform total IgA and TTG‑IgA (TG2‑IgA) as the preferred initial test in individuals ≥2 years; ensure testing is done while the individual is on a gluten-containing diet

Society guidance: ACG/AGA/ESsCD/ESP-GHAN/NASPGHAN

When to use IgG-based testing: If total IgA is low or IgA deficiency is suspected, perform IgG-based tests (IgG DGP, IgG TTG, or IgG EMA) as recommended by multiple societies

Biopsy indications: Recommend upper endoscopy with multiple duodenal biopsies for symptomatic patients with positive serology, patients with clinical presentation consistent with celiac disease even if serology is negative, or patients with lack of clinical response/relapse despite gluten-free diet

Ensure adequate gluten intake before testing

Diagnosis and monitoring criteria

Guidance and coverage-aligned criteria from multiple societies; apply when evaluating testing/diagnosis of suspected CD

Initial serologic testing: Use IgA anti-tTG (TG2-IgA) as the preferred first-line serologic test and measure total IgA concurrently; if IgA deficiency, use IgG-based tests (IgG-DGP or IgG-TTG)

Source societies: WGO, ESsCD, AGA

Indications for testing: Test symptomatic patients with gastrointestinal or extraintestinal features (eg, diarrhea, weight loss, iron deficiency anemia, elevated transaminases) and patients with associated conditions (eg, type 1 diabetes, autoimmune thyroid disease, Down syndrome) and first-degree relatives

Sources: ESsCD, ESP-GHAN, WGO

Endoscopic biopsy criteria (adults): In adults and most patients, positive serology or strong clinical suspicion warrants upper endoscopy with multiple duodenal biopsies (at least 4 from distal duodenum plus 1–2 from the duodenal bulb); ensure adequate gluten intake prior to testing

Sources: BSG, NASSCD, ESP-GHAN

The policy explicitly excludes certain categories of tests from coverage. Panel, multiplex, or multi-analyte testing for more than two analytes used to diagnose or evaluate celiac disease does not meet coverage criteria. Rapid antigen point-of-care tests for anti-TTG are also excluded. Additionally, testing for anti-reticulin antibodies and testing of stool or saliva samples for celiac disease evaluation are listed as not meeting coverage criteria. Finally, serologic assays that use an HLA-DQ–gluten tetramer–based method (including flow cytometry–based tetramer assays) are not covered.

Conventional anti-gliadin antibody tests (native gliadin assays) and antibody testing of stool or faecal samples are not recommended for primary diagnosis of celiac disease and therefore do not meet coverage criteria. Guideline panels note that anti-gliadin assays should not be used for diagnosis, and fecal/faecal antibody tests are specifically discouraged as they are not validated for diagnosing CD.

Urine, stool, or saliva measurements for celiac disease are not recommended for clinical practice because these sample types have demonstrated lower performance than blood-based serologic tests and therefore are not appropriate for routine diagnostic use.

As of July 2019, no nucleic-acid–based test solely for celiac disease had FDA approval. This policy notes the regulatory status to emphasize that nucleic-acid assays for exclusive celiac diagnosis were not FDA-approved at that time.

Certain tests are stated to not meet coverage criteria because of an insufficient published evidence base demonstrating clinical benefit. Examples include rapid point-of-care anti-TTG assays, panel/multiplex tests for >2 analytes, anti-reticulin antibody testing, and stool or saliva antibody tests. The policy cites the lack of available published scientific literature as the reason these tests are excluded from coverage.

Routine HLA‑DQ2/DQ8 genotyping is not medically necessary for initial diagnosis or broad screening because these alleles are common in the general population (present in roughly 25%–40% of people), which results in a low positive predictive value. HLA testing is reserved for selected clinical situations where its high negative predictive value helps to exclude disease (for example, discrepant serology/histology, prior gluten-free diet before testing, or equivocal histology).

Therapeutic trials of a gluten-free diet are not an indicated diagnostic approach when celiac disease is suspected. Professional guidance states that anti‑tTG positivity alone is insufficient for diagnosis, and clinicians should pursue appropriate serologic, genetic, or histologic evaluation rather than using a GFD trial as a diagnostic test.

Coding and Test Thresholds

TGA‑IgA threshold for no‑biopsy diagnosis (ESPGHAN pediatric threshold)

ESP‑GHAN pediatric no‑biopsy thresholdTGA‑IgA (tissue transglutaminase IgA) ≥ 10× upper limit of normal (ULN)

Assay requirementOnly antibody tests with proper calibrator curve-based calculation and measurement range that includes 10× ULN should be used

Confirmation step for childrenWhen TGA‑IgA ≥10× ULN in children, a second blood sample with positive EMA‑IgA is required for no‑biopsy diagnosis

tTG threshold for pediatric no‑biopsy diagnosis (>=10× ULN)

Pediatric tTG threshold for no‑biopsy pathway>= 10× ULN for tTG (tissue transglutaminase) in children

Action after high titerObtain further blood sample to check IgA‑EMA and determine HLA‑DQ2/DQ8; if EMA+ and compatible HLA, biopsy may be omitted

Provider Actions, Documentation, and Operational Rules

Documentation Required

Coverage-required tests and preferred testing sequence

Preferred initial testing: order IgA anti-tissue transglutaminase (IgA‑tTG) with total serum IgA for symptomatic individuals or those at risk. If total IgA is low or IgA deficiency is suspected, use IgG‑based tests (IgG DGP, IgG TTG, or IgG EMA) instead. For children under age 2, include DGP (IgA and IgG) in addition to IgA‑tTG. Genetic HLA DQ2/DQ8 testing may be used to help rule out disease in selected situations (e.g., equivocal histology, prior gluten-free diet without prior testing, discrepant serology/histology, or to exclude disease in high-risk individuals).

Coverage-required tests: IgA anti‑TTG + total IgA (preferred single test >2 years)
If IgA deficiency: IgG EMA, IgG DGP, or IgG TTG
Children <2 years: include IgA and IgG DGP alongside IgA‑TTG
HLA DQ2/DQ8: use to rule out in selected clinical scenarios (not for routine initial diagnosis)

Documentation Required

Endoscopy referral for confirmation

Symptomatic patients with positive or borderline serology should be referred for upper endoscopy with multiple duodenal biopsies to confirm or exclude celiac disease. For adults and most patients, duodenal biopsy remains the diagnostic standard. In those with tTG ≥10× ULN, follow guidelines for additional serology (EMA) and HLA testing and consider no‑biopsy confirmation in appropriate pediatric cases with required documentation (see pediatric no‑biopsy callout).

Background and Scope

Background: Celiac disease is an autoimmune disorder triggered by gluten ingestion that causes immune-mediated injury to small intestinal villi and impaired nutrient absorption. Presentation ranges from classic malabsorption and failure to thrive in children to abdominal pain, altered bowel habits, bloating, iron-deficiency anemia, or elevated liver enzymes in adults. Genetic markers HLA‑DQ2 and DQ8 confer susceptibility but are common in the population and thus are insufficient alone to confirm disease. Prevalence estimates are approximately ~1% worldwide, with about 2 million Americans estimated to have celiac disease.

Definitions and Test Descriptions

TTG (tissue transglutaminase) — primary recommended initial serologic test (IgA anti-TTG)

Test nameIgA anti‑tissue transglutaminase (IgA anti‑TTG)

RolePreferred single initial serologic test for detection of celiac disease in individuals ≥2 years

Paired measurementMeasure total IgA concurrently to detect IgA deficiency

DGP (deamidated gliadin peptides) — IgA/IgG antibodies

Test nameDeamidated gliadin peptide (DGP) antibodies — IgA and IgG

Use casesEspecially useful in children <2 years and in individuals with IgA deficiency (use IgG‑based DGP)

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyCeliac Disease Testing

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionOrder IgA anti-TTG with total IgA as the preferred initial test and document signs/symptoms or risk status when requesting testing.

SourceLink

On This Page

Serologic testing using an HLA-DQ-gluten tetramer-based assay, including flow cytometry-based assays, does not meet coverage criteria

Pediatric no-biopsy pathway:

In children, diagnosis without biopsy may be considered when TGA‑IgA ≥10× ULN confirmed by positive EMA‑IgA on a second sample with shared decision-making; use assays able to measure 10× ULN

TGA‑IgA >= 10× ULN

Require second-sample EMA confirmation and shared decision-making with parents/patient

Use of HLA testing: HLA‑DQ2/DQ8 testing should not be used routinely; reserve to effectively rule out celiac disease in select situations (eg, equivocal histology, seronegative with histologic changes, prior gluten-free diet without testing, discrepant serology/histology, suspicion of refractory CD, or certain pediatric contexts)

Dietary requirements for testing: Serologic testing and biopsies should be performed while the individual is on a gluten-containing diet; if the patient started a gluten-free diet, consider a gluten challenge (eg, ~1–3 months or per society guidance) before repeat testing

AGA suggests ~1–3 months with 3 slices of wheat bread daily before retesting

No-biopsy pathway (children): In symptomatic children with tTG ≥10× ULN plus positive EMA and compatible HLA-DQ2/8, diagnosis may be made without duodenal biopsy>=10x ULN

Source: ESsCD and BSPGHAN guidance; require EMA confirmation on second sample and shared decision-making

Follow-up monitoring: Antibody monitoring (anti-tTG IgA or anti-DGP IgG in IgA deficiency) is recommended after 3–6 months in the first year and annually thereafter in stable patients on a gluten-free diet3-6 months then yearly

Source: WGO and society guidance

If tTG elevated but <10× ULNDuodenal biopsy is required

FDA approval date referenced for Aptiva reagent

Aptiva reagent FDA clearance dateJune 16, 2021

Device descriptionAptiva Celiac Disease IgA Reagent: particle-based multi-analyte immunoassay for semi-quantitative determination of anti‑tTG IgA and anti‑DGP IgA in serum

IndicationCan be used to diagnose celiac disease and dermatitis herpetiformis per FDA clearance

Refer symptomatic patients with positive or borderline serology for endoscopy with multiple duodenal biopsies
Endoscopy/biopsy is recommended for confirmation in high‑risk individuals regardless of serology

Note

Test platforms, FDA approvals, and excluded test types

Use FDA‑cleared/approved serologic assay platforms when available. Examples of FDA‑cleared systems include multiple ELISA and multiplex platforms (Inova Quanta Lite/Quanta Plex, Phadia EliA Celikey, Bioplex 2200, FIDIS, IMMULISA, SQI IgPlex, Aptiva multi‑analyte assay). Panel/multiplex tests that include >2 analytes for celiac evaluation are not covered.

Use FDA‑cleared assays where available (see FDA approvals list)
Panel/multiplex tests >2 analytes for diagnosis are not covered
Rapid point‑of‑care anti‑TTG tests are not covered

Documentation Required

Diet requirement for accurate testing

All serologic testing should be performed while the individual is consuming a gluten‑containing diet to avoid false‑negative results. If the patient has been on a gluten‑free diet prior to testing, document attempts to reintroduce gluten and consider HLA testing or referral for specialist evaluation. Ensure adequate gluten intake before biopsy sampling; coordinate with a dietician as needed.

Testing must be done on a gluten‑containing diet for accurate results
If already on a gluten‑free diet, document dietary history and management steps taken prior to testing/biopsy

Documentation Required

LDT validation and CLIA compliance

Laboratory‑developed tests (LDTs) used for celiac serology must be validated and performed in CLIA‑certified high‑complexity laboratories. Document test provenance (FDA‑cleared vs LDT) and evidence of validation/CLIA compliance when ordering or billing for non‑FDA‑cleared assays.

LDTs: must be validated and performed under CLIA high‑complexity rules
Document whether assay is FDA‑cleared or an LDT and include validation/CLIA details in laboratory records

Documentation Required

Clinical documentation to support testing

When ordering celiac serology or HLA testing, document clinical indications: signs/symptoms consistent with celiac disease, high‑risk conditions (e.g., type 1 diabetes, Down syndrome, autoimmune liver disease, first‑degree relative with celiac), or specific clinical questions (e.g., ruling out disease on GFD, discrepant results). Record relevant prior test results, diet history (gluten exposure), and rationale for chosen tests.

Include signs/symptoms or high‑risk status in medical record when ordering tests
Document prior serology/histology, gluten diet status, and reason for HLA testing when applicable

Documentation Required

No‑biopsy pediatric confirmation documentation

Pediatric no‑biopsy pathway: for children with tTG ≥10× ULN, a shared decision‑making no‑biopsy diagnosis may be acceptable if a second blood sample confirms positive IgA EMA and the family accepts the approach. Ensure documentation of tTG level, repeat EMA result, discussion of risks/benefits, and agreement from patient/guardian.

No‑biopsy pediatric confirmation requires tTG ≥10× ULN and positive EMA on a second sample
Document shared decision‑making and retain serum for potential later testing if EMA not locally available

Documentation Required

Biopsy sampling and pretest dietary status

Biopsy sampling: obtain at least four biopsies from distal duodenum (D2 or lower) and at least one biopsy from the duodenal bulb to capture patchy disease. Ensure biopsies are taken while the patient is on a gluten‑containing diet and are properly oriented for histology; consider re‑cutting or expert pathology review if results are discordant.

At endoscopy take ≥4 biopsies from distal duodenum plus ≥1 from duodenal bulb
Confirm adequate gluten intake prior to biopsy and document diet status
Request re‑cutting or second pathology opinion for discordant serology/histology

Step Therapy

Step therapy

No step therapy is specified in this policy.

Anti‑DGP may detect some tTG‑negative patients but has lower specificity in some groups (higher false positives in infants)

HLA DQ2/DQ8 — genetic alleles associated with susceptibility

Genetic markersHLA‑DQ2 and HLA‑DQ8 alleles (DQ2 encoded by DQA1*05/DQB1*02; DQ8 encoded by DQA1*03/DQB1*03:02)

Clinical utilityUseful to effectively rule out celiac disease when absent (high negative predictive value)

LimitationsPresent in ~25–40% of general population; positive result has low positive predictive value and should not be used for routine initial screening

High‑titer tissue transglutaminase IgA — defined threshold (TGA‑IgA ≥10× ULN)

DefinitionHigh‑titer tissue transglutaminase IgA defined as TGA‑IgA ≥ 10× upper limit of normal (ULN)

ImplicationSupports pediatric no‑biopsy diagnostic pathway when combined with confirmatory EMA and compatible HLA

Assay requirementUse assays with calibrator curves and measurement ranges that include 10× ULN

HLA‑DQ2/DQ8 testing interpretive note

NPV vs PPVHLA‑DQ2/DQ8 typing has high negative predictive value but low positive predictive value; absence makes CD very unlikely

Recommended useReserve testing for diagnostic dilemmas (eg, seronegative with histologic changes, prior GFD without testing, discrepant serology/histology)

Not routineNot recommended as routine initial diagnostic or screening test due to high population prevalence of variants

Anti-tTG IgA — first-line serologic test and need to pair with total IgA measurement

Test nameAnti‑tTG IgA (anti‑tissue transglutaminase IgA)

RoleFirst‑line serologic screening test for celiac disease

Concurrent testingShould be paired with measurement of total IgA to identify IgA deficiency

Anti-DGP — role and use-case (IgG-based in IgA deficiency)

Primary roleAnti‑DGP (IgG) is used when IgA deficiency is present or suspected

Pediatric useIncluded with IgA‑TTG testing for children <2 years or as an alternative when IgA deficiency is suspected

Performance caveatMay detect some tTG‑negative patients; specificity can be lower in infants

HLA‑DQ2/DQ8 typing — high negative predictive value; interpretive guidance

Negative predictive valueA negative HLA‑DQ2/DQ8 result effectively excludes celiac disease (high NPV)

Positive resultA positive HLA result does not confirm disease due to high background prevalence of these alleles

Recommended contextsUse in diagnostic dilemmas, before/after gluten‑free diet initiation, or when histology/serology are discordant

LDT — definition and regulatory context (CLIA '88 high-complexity)

DefinitionLaboratory‑developed test (LDT): a test developed and performed within a single laboratory that must be validated in‑house

RegulationLDTs are regulated by CMS as high‑complexity tests under CLIA '88; they are not FDA‑cleared/approved for clinical use unless separately submitted

Documentation requirementDocumentation should demonstrate LDT validation and CLIA high‑complexity compliance for clinical/reimbursement use

Aptiva Celiac Disease IgA Reagent — short definition and relevance (FDA-cleared reagent referenced)

NameAptiva Celiac Disease IgA Reagent

Short definitionAn FDA‑cleared particle‑based multi‑analyte immunoassay for semi‑quantitative determination of anti‑tTG IgA and anti‑DGP IgA in human serum

RelevanceCited as an example of an FDA‑cleared serologic assay platform usable for celiac disease diagnosis