What is the recommended algorithm for screening relatives of patients with coeliac disease (ceeliac disease)?

Family Screening Algorithm for Relatives of Celiac Disease Probands

First-degree relatives (parents, siblings, children) of patients with celiac disease should undergo serological screening with IgA tissue transglutaminase (tTG) antibodies plus total serum IgA levels, regardless of symptoms, given their 4.8-10% prevalence of celiac disease compared to 0.3-1% in the general population. 1, 2

Initial Screening Protocol

Who to Screen

• All first-degree relatives (parents, siblings, children) of confirmed celiac disease patients should be offered screening 3, 1, 4
• Consider screening second-degree relatives if they are symptomatic or have other autoimmune conditions 3
• Prioritize symptomatic relatives who have gastrointestinal complaints, unexplained anemia, growth failure, or other suggestive features 1, 4

Initial Testing Approach

• Measure IgA tissue transglutaminase (tTG-IgA) antibodies with documentation of normal total serum IgA levels as the primary screening test 3, 1, 5
• If IgA deficiency is present, use IgG tTG and deamidated gliadin peptide antibodies instead 3, 5
• Testing must occur while the relative is consuming a gluten-containing diet to avoid false-negative results 1, 4

Confirmatory Steps for Positive Serology

• Duodenal biopsy remains essential for diagnosis confirmation in adults and most children with positive antibodies 3, 1
• Obtain at least 4-6 biopsy specimens from the second part of the duodenum or beyond, including the duodenal bulb 3, 1
• In children with tTG-IgA ≥10× upper limit of normal, positive endomysial antibodies, and positive HLA-DQ2/DQ8, biopsy may potentially be avoided per European guidelines, though this remains controversial 1, 5

HLA Typing Strategy

When to Use HLA Testing

• Consider HLA-DQ2/DQ8 testing at initial screening to stratify future risk and guide re-screening intervals 3, 1
• Absence of HLA-DQ2 and HLA-DQ8 effectively rules out celiac disease (high negative predictive value) and eliminates need for future screening 3, 1
• HLA typing is particularly useful for relatives who are reluctant to undergo repeated serological testing, as negative HLA can provide reassurance 3

Risk Stratification by HLA Status

• High-risk HLA genotypes (DQ2.5/2.5 or DQ2.5/2.2) warrant more frequent re-screening, as these individuals have higher conversion rates 6
• Relatives with positive HLA-DQ2/DQ8 but negative initial serology should undergo periodic re-testing 6

Re-Screening Protocol for Initially Negative Relatives

Timing of Re-Screening

• Repeat screening within 2 years of the initial negative test 3
• Re-screen again after 5 years from initial testing 3
• The annual incidence of seroconversion is approximately 221/100,000 person-years in all relatives and 336/100,000 in those with HLA-DQ2/DQ8 6

More Frequent Screening Indicated For:

• Relatives who develop symptoms suggestive of celiac disease (diarrhea, weight loss, abdominal pain, unexplained anemia) 3
• Younger relatives at initial screening (particularly those under age 25), as they have higher conversion rates 6
• Those carrying high-risk HLA genotypes (DQ2.5/2.5 or DQ2.5/2.2) 6
• Relatives with other autoimmune conditions such as type 1 diabetes or autoimmune thyroid disease 3, 1

Special Populations

Children and Adolescents

• Screen soon after diagnosis of the proband when the child is old enough for reliable testing 3, 5
• In children with type 1 diabetes who are first-degree relatives, consider more frequent screening given dual risk factors 3
• Monitor growth parameters closely as poor growth may indicate undiagnosed celiac disease 5

Asymptomatic Relatives

• Do not withhold screening based on absence of symptoms, as silent celiac disease is common and carries similar long-term complications including osteoporosis and potential malignancy risk 3, 4
• Approximately 75% of relatives with biopsy-proven celiac disease may be asymptomatic at diagnosis 4

Common Pitfalls to Avoid

• Only 39-50% of first-degree relatives actually undergo recommended screening in real-world practice, often due to inadequate documentation of family history 7
• Ensure family history of celiac disease is documented in the medical record to trigger appropriate screening 7
• Do not rely on endoscopic appearance alone—normal-appearing duodenum can still harbor villous atrophy 3
• Avoid testing relatives who have already started a gluten-free diet without prior evaluation, as this causes false-negative serology 1, 4
• False-positive sucrose permeability tests can occur with gastric erosions independent of celiac disease 8

Management of Newly Diagnosed Relatives

• Initiate strict gluten-free diet immediately upon biopsy confirmation 3, 5
• Refer to a dietitian experienced in celiac disease management for comprehensive dietary counseling 3, 5
• Screen for nutritional deficiencies including iron, folate, vitamin D, and vitamin B12 5
• Schedule follow-up every 6-12 months to monitor adherence and symptom resolution 5