Celiac Disease: The Importance of Family Screening

Contributed by: Lisa Fahey, MD and Arunjot Singh, MD, MPH Case: Jane is a 9-year-old twin female who presents to per primary care pediatrician’s office with abdominal pain, fatigue, and increased pallor over the past month. Pain is nonradiating and localized to the periumbilical region. She reports intermittent nausea, but denies vomiting. She has been having hard stools, type 3 on the Bristol stool scale, once daily, without blood or mucous. On initial examination, she is afebrile and vital signs are stable. She appeared mildly pale but is in no acute distress. Her abdomen is soft, nontender, with no masses or hepatosplenomegaly. The working diagnosis at the time of that visit is a viral illness, and she is discharged home with supportive care management.

Unfortunately, Jane continues to feel unwell with frequent visits to the school nurse over the next 2 weeks leading to a follow-up at her PCP. Although her exam remains unchanged, her growth chart shows a plateau in weight over the past 2 months which, given her symptoms, leads to more comprehensive testing. Screening labs ordered are notable for elevated tissue transglutaminase IgA (TTG IGA) level as well as an endomysial IgA antibody level, which sparks your suspicion for celiac disease and a referral to pediatric gastroenterology. 

Over the next several weeks, Jane meets with her gastroenterologist and undergoes an esophagogastroduodenoscopy with biopsy that confirms the diagnosis of celiac disease. As she begins her gluten-free journey, the family is counseled on the importance of family screening for celiac disease. Her three siblings have celiac serologies drawn, and all three have positive TTG IGA celiac panels. Interestingly, her twin sister, Emma, and brother, Joe, end up also being diagnosed with celiac disease on duodenal biopsy despite being asymptomatic. Their older sister, Kristen, reported reflux and intermittent dysphagia, which was significant for Candidal esophagitis on endoscopy, although her duodenal biopsies were negative for celiac disease.

Family Screening in Celiac Disease

Discussion: Celiac disease is an autoimmune enteropathy that affects approximately 1% of the general population. It is well established that genetics are a major contributory factor in a patient’s likelihood to develop celiac disease. Human leukocyte antigen (HLA) DQ heterodimers DQ2 and/or DQ8 are the primary genes identified to date, although it is important to recognize these are insufficient for diagnosis (up to 40% of the general population are positive for HLA-DQ2/8, but only 1% will actually develop celiac disease). In clinical practice, celiac HLA genotyping is most useful for elucidating challenging cases of suspected celiac disease and for its negative predictive value. Specifically, if a person is negative for both the DQ2 and DQ8 antigens, then it is very unlikely that they will develop celiac disease.

First-degree relatives of a patient with celiac disease have approximately a 10% risk of developing celiac disease in their lifetime. Because of this, celiac serologic screening is recommended for all first-degree family members, even if they are asymptomatic. Screening should always be done with individuals on a gluten-containing diet to reduce the risk of false negatives.

At CHOP’s Center for Celiac Disease, we recommend a celiac screening panel of TTG IgA, endomysial IgA and total immunoglobulin A in all first-degree family members of a child with celiac disease. We recommend this screen be done every 1 to 2 years starting at age 2 years old for siblings and continued until they reach puberty. After puberty, we recommend periodic screening every few years. In younger children and those with selective IgA deficiency, serologies such a deaminated gliadin IgG and tissue transglutaminase IgG may also be advised.

The decision of whether to order HLA genotyping for a patient with suspected celiac disease or their family member is made on a case-by-case basis. It can be useful in cases of diagnostic dilemma or if a family does not want a sibling to have repeated celiac serologies throughout their life. In this scenario, the patient with celiac disease should also have HLA genotyping in order to best understand the implications of the sibling’s HLA results.

Center for Celiac Disease’s Approach to Care

The Center for Celiac Disease at CHOP focuses on a collaborative approach to provide specialized care for children with celiac disease, wheat allergy and non-celiac gluten sensitivity. Our team includes expert physicians, nurse practitioners, dieticians, nurse educators, psychologists, and social workers. In addition to coordinated clinic visits with expert clinicians and dieticians—with more than 1,096 families cared for last year—we also offer celiac education classes for our newly diagnosed celiac disease patients and their families.

In addition, the center participates in numerous clinical and translational research studies as well as quality improvement initiatives using health technology to optimize disease surveillance and clinical pathways.

Finally, all—physicians and your patient families—are invited to attend our 16th annual Celiac Education Day on March 7, 2021, which will be virtual this year with the theme of managing celiac disease in everyday life. Check chop.edu/celiac for more information on Celiac Education Day.

Celiac Family Screening Recommendations

Siblings ≥ 2 years old

Screening Markers: TTG IGA, Endomysial antibody IGA, Total IGA
Screening Frequency: Every 1-2 years until puberty, then every 3-5 years

Siblings under 2 years old

Screening Markers: Routine screening not recommend if asymptomatic. If symptomatic, add DGP-IGG to above panel.
Screening of Frequency: N/A

Biological parents

Screening Markers: TTG IGA, Endomysial antibody IGA, Total IGA
Screening Frequency: Every 3-5 years

** Note: If individual is identified to have selective IgA deficiency, then deamidated gliadin IgG, tissue transglutaminase IgG, and endomysial antibody IGG, in addition to total IGG, is advised for accurate celiac disease screening.