Close Relatives of Celiac Disease Patients at Higher Risk

Ricki Lewis, PhD

August 23, 2019

First-degree relatives of people who have celiac disease (CD) are at elevated risk of developing the condition — although they may have no symptoms — and could benefit from screening, according to results of a study published online August 22 in Mayo Clinic Proceedings.

About 1% of the US population has CD, but others may have it and be asymptomatic. Diagnosis is based on elevated serological markers such as anti-tissue transglutaminase antibodies (anti-TTG; IgA and IgG) and endoscopy to examine and biopsy the small intestine lining.

Previous studies have shown first-degree relatives of people diagnosed with CD face as much as an 11% risk of developing it, too. However, the US Preventive Services Task Force recommendations restrict screening to symptomatic first-degree relatives, although studies have shown that close relatives can have CD without symptoms.

Shilpa S. Nellikkal, MBBS, of the Division of Pediatric Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota, and colleagues conducted a retrospective cohort study to assess the prevalence of diagnosed CD among first-degree relatives screened for elevated anti-TTG. The investigation also compared the sensitivity of the marker with that of small bowel biopsy.

Using data from Mayo Clinic electronic records and a CD registry spanning December 1983 to May 2017, the researchers evaluated 104 patients diagnosed with CD and their first-degree relatives (parents, siblings, and children). They considered symptoms, demographics, family history, number of other family members screened for CD, biopsy reports, and serology findings.

Classic symptoms of CD are weight loss and diarrhea or failure to thrive in children, and weight loss and diarrhea in adults. Nonclassic symptoms are nonspecific abdominal pain, bloating, flatulence, anemia, constipation, headache, poor dental enamel, and osteoporosis, as indicated in the medical records. The third category in the study was asymptomatic.

Of 477 first-degree relatives of the 104 patients, 360 individuals had been screened for CD and of these 160 (44%) were diagnosed and tested positive for anti-TTG titer. Of the 160 diagnosed relatives, 148 presented with clinical features of CD, but only nine (6%) had classic symptoms, whereas 97 (66%) had nonclassic symptoms and 42 (28%) reported no symptoms. Therefore, 94% of the positive-testing first-degree relatives did not have classic CD.

Mean age at diagnosis was 31.9 ± 21.6 years, and 62% of the first-degree relatives with CD were female.

Histology reports of crypt hyperplasia and villous atrophy for intestinal biopsies on 155 of the relatives showed that 12 (8%) had Marsh 1 classification, 77 (50%) had Marsh 3a, and 66 (43%) had Marsh 3b.

An anti-TTG level ≥ 2.75 of the upper limit of normal had 87% sensitivity, 82% specificity, and a positive predictive value of 95% for identifying first-degree relatives with villous atrophy. High anti-TTG titer was positively associated with villous atrophy on small bowel biopsies, irrespective of symptoms.

Medical records indicated the median time for diagnosis of a first-degree relative from diagnosis of the index patient was approximately 6 months.

Lead author Imad Absah, MD, also of the Mayo Clinic, advised in a news release that "gastroenterologists and general practitioners should ask about any family history of celiac disease among their patients' parents, siblings and children" and offer screening if these individuals are present during the clinic visit.

Screening to detect CD before symptoms arise for those at elevated risk as a result of family history could help prevent long-term complications such as nutritional deficiencies and speed detection of intestinal cancer and development of new autoimmune conditions, the researchers write.

The positive association between high anti-TTG titer and villous atrophy supports the need for screening all first-degree relatives of people with CD, including those without symptoms, the investigators conclude. They call for larger multicenter prospective studies to confirm anti-TTG titer as a diagnostic test for first-degree relatives, which could minimize the need for biopsy.

Limitations of the study include the retrospective design, referral bias from a tertiary care center, and limited follow-up of patients.

The researchers have disclosed no relevant financial relationships.

Mayo Clinic Proc. Published online August 22, 2019. Full text

Follow Medscape on Facebook, Twitter, Instagram, and YouTube.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.