Celiac disease registry at University of Alabama reveals potential issues in celiac disease diagnosis
By Amy Ratner, director of scientific affairs
In a new registry of celiac disease patients at the University of Alabama at Birmingham, Black people with biopsy confirmed celiac disease were more likely than non-Hispanic whites to have had negative results on the most commonly used diagnostic blood test, according to a presentation made recently at Digestive Disease Week.
The anti-tissue transglutaminase immunoglobulin A (TTG) blood test is usually the first step toward a celiac disease diagnosis, said Amanda Cartee, MD, a gastroenterologist at the university who presented registry data at DDW. A positive TTG test will often trigger an endoscopy and biopsy to confirm celiac disease.
The registry findings on blood test results raise the question of whether further confirmatory testing for celiac disease is deterred in Black people in general clinical practice, Cartee said.
Eighty percent of Black patients with biopsy-confirmed celiac disease in the registry had TTG test results that were less than the upper limit of normal, compared to about 9 percent of non-Hispanic white patients in the registry. The upper limit of normal is the highest level at which a test result is still considered in the normal range. A result higher than the upper limit of normal is considered positive.
Black patients were also much less likely to have been tested for the genes associated with celiac disease.
The high sensitivity of the TTG test is called into question by the findings in the registry, Cartee said, adding that 5 percent of the patients in the registry self-reported being Black. “These patients are more likely to have [serology]-negative disease,” she said.
Black patients in the registry were also more likely than non-Hispanic whites to have a greater Body Mass Index (BMI) at diagnosis. “In classic celiac disease, we tend to think of patients as having low or low normal BMI,” Cartee said. “However, with the US obesity epidemic, and then changing clinical presentation of celiac disease, we are seeing higher BMI as a diagnosis.”
Cartee noted that at 46 percent, Alabama has the highest self-reported rate of obesity among Black people in the United States, according to the Centers for Disease Control. “It is really no surprise to us that [Black people} in our registry have a [high] BMI at diagnosis,” she said.
While there were differences in TTG test results and BMI, non-Hispanic white and Black patients in the registry had similarities in celiac disease diagnosis. These included symptoms as the primary cause for testing, length of time to diagnosis and diagnosis that did not follow recommended guidelines that call for blood tests and a biopsy.
There is limited data on celiac disease and Black people, Cartee said, noting that only a single study with the primary goal of investigating the clinical characteristics of celiac disease and Black people has been done.
The University of Alabama Birmingham, located in a part of the state with significant socioeconomic and health disparities, has a diverse patient referral base, she said. Black people make up 25 percent of the population of Alabama, more than twice than in the general US population.
With this in mind, Cartee and colleagues created the celiac disease registry to determine the proportion of patients in various self-identified racial groups, focusing primarily on Black patients and non-Hispanic whites, and determine if there were differences between the two groups at diagnosis, including symptoms, diagnostics and BMI.
Investigators reviewed billing codes in the university medical records from 2011 to 2021 to ultimately determine that 852 patients had potential celiac disease. About 90 percent, 700 patients, self-identified as non-Hispanic white, and slightly less than 5 percent, 42 patients, self-identified as Black.
Patients in the registry were categorized as having possible, probable and definite celiac disease based on information used to diagnose celiac disease. This ranged from those on the gluten-free diet without any testing to those who had records of having blood tests and a biopsy.
Those categorized as possible had: symptom resolution on the gluten-free diet; were on the gluten-free diet without having had any celiac disease tests; had mildly positive celiac disease blood test results or had negative results while already on a gluten-free diet; had a diagnosis from another medical institution without information about how the diagnosis was made; or listed gluten or gluten-containing grains as allergies. About 54 percent of non-Hispanic white patients met one of these criteria, as did about 67 percent of Black patients.
About 18 percent of non-Hispanic whites and about 10 percent of Black patients were categorized as having probable celiac disease based on TTG blood test results that were four times the upper limit of normal or greater or if an outside diagnosis mentioned a biopsy follow-up to positive blood tests or suggested video capsule endoscopy findings.
Those with biopsy proven celiac disease with records that included biopsy findings were classified as definite celiac disease. About 32 percent of non-Hispanic white patients and about 24 percent of Black patients in the registry fit this category.
Overall, there were no statistically significant differences in the proportion of non-Hispanic whites and Black people in each of the subgroups, Cartee said.
Symptoms, both gastrointestinal and others, were the primary reason both non-Hispanic whites and Black people were tested for and diagnosed with celiac disease, according to the registry.
Positive tests for anemia and elevated liver function similarly led to celiac disease testing and diagnosis in both groups.
But for Black patients, tests that indicated osteopenia or osteoporosis, which can be related to celiac disease, did not lead to celiac disease testing. Likewise, family history of celiac disease, other related conditions with a high risk of celiac disease, including type 1 diabetes, or suspicious results of an endoscopy prompted by something other than celiac disease did not lead to celiac disease testing or diagnosis.
Symptoms in Black patients in the definite celiac disease subgroup might have been more profound or severe given that they went on to have endoscopies with biopsies even when blood tests for celiac disease were negative, Cartee said,
Guidelines for diagnosis of celiac disease in the United States, which call for celiac disease blood tests and a biopsy, were used in only about half of patients in the registry, highlighting a contrast between the guidelines and clinical practice reality, Cartee said.
About 28 percent of non-Hispanic white and 38 percent of Black patients in the registry were diagnosed based on either symptom resolution on the gluten-free diet alone or blood tests alone, some of which might have been only borderline positive.
Compared to non-Hispanic whites, about double the percent of Black patients were diagnosed on symptom resolution alone. Though the total number of Black patients was small, this might signal that they tried the gluten-free diet on their own after getting negative results on the TTG blood test, Cartee said.
Celiac disease and race
“The registry is unique because it includes patients with known and potential celiac disease who self-identify as Black,” Cartee said. “We hope to provide insight into differences in celiac disease presentation, diagnosis, complications and treatment response between Black patients and non-Hispanic white patients.”
Despite an overall lack of race-related data, some issues in celiac disease diagnosis in racial and ethnic minorities have been investigated. A 2021 study found that Black people, as well as those with public health insurance, who went to the doctor with iron deficiency anemia and chronic diarrhea had about 90 percent decreased odds of having the appropriate follow-up. The study suggested patients with celiac disease may go undiagnosed, the study authors wrote.
Racial disparities in celiac disease and other autoimmune diseases have been found in other research as well, including a 2012 study that found Black patients with diarrhea, anemia, iron deficiency or weight loss were less likely to have a duodenal biopsy than younger people, women and whites. A recent study by researchers from University of Southern California found that Black people and Latinos with multiple sclerosis and other autoimmune diseases experience health disparities such as greater disease severity and faster disease progression than white Americans.
Although celiac disease has long been thought to affect predominantly Caucasian populations, a major 2018 systematic review that looked at data from 1991-2016 on 275,000 individuals with celiac disease concluded that it is a major public health problem worldwide.
Meanwhile, a 2015 National Health and Nutrition Examination Survey (NHANES) study that looked at results of two blood tests for celiac disease in about 15,000 participants but did not include biopsy results found that celiac disease autoimmunity was four times higher among non-Hispanic whites than in non-Hispanic Black people, about 1 percent compared to about .2 percent. The study included the more common TTG test and the endomysial antibody (EMA) test. Celiac disease autoimmunity was defined as a fully positive TTG and/or EMA, or dual weakly positive blood tests.
Higher rates of negative TTG blood test results in Black patients with biopsy confirmed celiac disease raise questions about the ability to perform population-based studies such as NHANES that rely on blood test results alone in minorities in the United States, Cartee noted. This underscores the importance of inclusive studies in celiac disease, she concluded.
Beyond Celiac diversity project
Up to 80 percent of those with celiac disease remain undiagnosed. The likelihood of being diagnosed could be influenced by race and ethnicity because of access to medical care, referral bias and other factors.
Beyond Celiac has partnered with the National Minority Quality Forum to examine and address health inequities in the diagnosis and treatment of celiac disease. The joint project aims to increase awareness of the prevalence of celiac disease in the United States and to investigate the extent of undiagnosed celiac disease in diverse populations.
At DDW, Beyond Celiac presented data showing racial and ethnic healthcare disparities in celiac disease diagnosis indicated by analysis of geographic and demographic distribution of celiac disease in the United States. The analysis was based on evidence from 2016 Medicare and Medicaid fee-for-service claims.
More than 70,000 Medicare beneficiaries had at least one celiac-disease-related claim in 2016. They were located primarily in the Northeast and Midwest. Meanwhile potentially undiagnosed celiac disease, based on beneficiaries with combined claims for irritable bowel syndrome (IBS) and anemia, showed the opposite geographic distribution, with beneficiaries primarily located in the South and East. Nearly 11,000 Medicare beneficiaries had these combined claims.
This may suggest some of these beneficiaries have celiac disease and are misdiagnosed, the study says, noting that celiac disease centers with gastroenterologists and dietitians with expertise in celiac disease are located primarily in the Northeast and Midwest and may play a role in increased diagnosis.
Most eligible beneficiaries in both Medicare and Medicaid with a celiac disease claim in 2016 were white, nearly 93 percent in Medicare and about 63 percent in Medicaid. However, Medicaid beneficiaries were more racially diverse, with a greater percentage Black and Hispanic individuals. Nearly 6 percent of those with celiac disease claims were Black compared to about 3 percent in Medicare. About 11 percent in Medicaid were Hispanic, compared to 1 percent in Medicare.
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