Currently accepted indications for celiac disease testing are ineffective and fail to discriminate between patients with and without undiagnosed celiac disease, according to a case-control study in
Alimentary Pharmacology and Therapeutics. Although almost 40% of a 400-patient cohort had at least one testing indication, the study found that fewer than 5% of the patients were actually tested for celiac disease — suggesting, the authors said, a strong need for alternative methods of detecting symptomatic celiac disease.
“This is a novel and clinically relevant finding,” the study’s senior author, Alberto Rubio-Tapia, MD, of the Mayo Clinic in Rochester, Minn., told MedPage Today. “Celiac disease remains one of the most unrecognized disorders among physicians despite better awareness about the disease in the public.”
The study also found that individuals with undiagnosed celiac disease were more likely to develop indications for testing such as osteoporosis and autoimmune conditions.
The researchers noted that celiac disease is significantly underdiagnosed, with clinical testing currently guided by case finding. While this condition affects 1% of North Americans and Western Europeans, an estimated
83% of cases in the United States go undiagnosed, showing a lack of awareness among clinicians and the ambiguous nature of symptoms, the team said.
In 2017, a U.S. Preventive Services Task Force
recommendation judged the evidence supporting targeted screening of asymptomatic persons to be insufficient.
Rubio-Tapia et al based their case-control study of adults with no prior celiac disease on serum samples from patients treated by the Mayo Clinic during 1995-2009 and residing in Olmsted County, Minn.
Blinded reviewers identified undiagnosed cases through sequential serology, and cases were matched by age and gender to unaffected controls. Medical records were reviewed for indications for and evidence of clinical testing.
In a cohort of 47,557 adults, 400 cases of undiagnosed celiac disease were identified and matched to 400 serology-negative controls. In the cohort, 61% were female and median age was 44.2.
While 38.3% of the cases (n=306) had at least one indication for testing, only 4.4% (n=35) were tested in the community setting before serologic testing. And testing was less frequently done in undiagnosed celiac disease, with nine cases (2.3%) tested, as opposed to 26 controls (6.5%), for an odds ratio (OR) of 0.32 (95% CI 0.14 to 0.71, P=0.005).
Serologic testing was similar between the cases and controls: OR 0.583 (95% CI 0.23 to 1.48, P=0.26), but small-bowel biopsies were significantly more likely in controls: OR 0.06 (95% CI 0.01 to 0.42, P=0.005).
Classical and non-classical symptoms and signs associated with celiac disease included vitamin and iron deficiency, anemia, iron deficiency (P=0.001), diarrhea, chronic diarrhea, recurrent abdominal pain, bloating, and incidental villous atrophy. Other indicators were dermatitis herpetiformis, hypothyroidism, infertility, chronic fatigue, vitiligo, a family history of celiac disease, and type 1 diabetes mellitus.
Serologic status was not associated with having an indication for testing, and 38.8% of cases and 37% of controls had some indication: OR 1.18 (95% CI 0.85 to 1.63, P=0.32). The number of indications for testing per individual was also similar between the two groups.
While most indications for clinical testing did not differ significantly between cases and controls, hypothyroidism was significantly more likely in those with undiagnosed celiac disease: OR 2.07 (95% CI 1.12 to 3.83, P=0.02).
Undiagnosed celiac disease cases were less likely to have dyspepsia and chronic diarrhea, but more likely to develop comorbid conditions such as osteoporosis (P=0.005), dermatitis herpetiformis (P=0.006), chronic fatigue (P=0.033), thyroiditis (P=0.003), and autoimmune diseases (P=0.008), as well as more likely to have family member with a diagnosis of celiac disease (P=0.001).
“Even if you apply the current paradigm to perfection, detection may improve a bit, but most cases will remain undiagnosed and a large number of persons without the disease may be exposed to the risk of testing to detect a minority of cases with celiac disease,” Rubio-Tapia said,
New strategies for clinical detection are urgently needed, he emphasized. “The challenge is to increase detection among celiac disease cases and also to reduce the number of persons without celiac disease exposed to testing. Gastroenterologists should think about celiac disease more broadly — not just as a gastrointestinal condition but also as a systemic disorder with multiple clinical presentations. [Clinicians] should have a low threshold for testing for celiac disease that is not just limited to traditional high-risk groups, since this study strongly suggests that most cases will remain undiagnosed following the current paradigm of case-finding.”
The researchers noted that study limitations included the fact that undiagnosed celiac disease was identified through sequential serology only, since duodenal biopsies were not available because of a lack of contact with participants. In addition, serology was tested at a random point of time in a given participant’s medical history, yet there has been evidence of seropositivity regression in the pediatric population.
Another potential limitation was that the study did not identify immunoglobulin A deficiency, which can lead to a false-negative immunoglobulin A tissue transglutaminase antibody, leading to possible misclassification of an estimated nine individuals in the cohort of 47,577, Rubio-Tapia et al continued. Nor did the study identify patients on a gluten-free diet, which might have led to false-negatives in a small number, since the collection years predated the trend to gluten-free diets.
The study received funding from the National Institutes of Health.
The authors reported having no conflicts of interest.
Primary Source
Alimentary Pharmacology and Therapeutics
