Prevalence and Morbidity of Undiagnosed Celiac Disease From a Community-Based Study

Abstract

Background & aims: Little is known about the prevalence and burden of undiagnosed celiac disease in individuals younger than age 50. We determined the prevalence and morbidity of undiagnosed celiac disease in individuals younger than age 50 in a community.

Methods: We tested sera from 31,255 residents of Olmsted County, Minnesota (<50 y), without a prior diagnosis of celiac disease assay using an assay for IgA against tissue transglutaminase; in subjects with positive test results, celiac disease was confirmed using an assay for endomysial IgA. We performed a nested case-control study to compare the proportion of comorbidities between undiagnosed cases of celiac disease and age- and sex-matched seronegative controls (1:2). Medical records were abstracted to identify potential comorbidities.

Results: We identified 338 of 30,425 adults with positive results from both serologic tests. Based on this finding, we estimated the prevalence of celiac disease to be 1.1% (95% confidence interval, 1.0%-1.2%); 8 of 830 children tested positive for IgA against tissue transglutaminase (1.0%; 95% confidence interval, 0.4%-1.9%). No typical symptoms or classic consequences of diagnosed celiac disease (diarrhea, anemia, or fracture) were associated with undiagnosed celiac disease. Undiagnosed celiac disease was associated with increased rates of hypothyroidism (odds ratio, 2.2; P < .01) and a lower than average cholesterol level (P = .03) and ferritin level (P = .01). During a median follow-up period of 6.3 years, the cumulative incidence of a subsequent diagnosis with celiac disease at 5 years after testing was 10.8% in persons with undiagnosed celiac disease vs 0.1% in seronegative persons (P < .01). Celiac disease status was not associated with overall survival.

Conclusions: Based on serologic tests of a community population for celiac disease, we estimated the prevalence of undiagnosed celiac disease to be 1.1%. Undiagnosed celiac disease appeared to be clinically silent and remained undetected, but long-term outcomes have not been determined.

Keywords: Autoimmune Disease; Epidemiology; Mortality; Small Intestine.

Figure 1

The prevalence of undiagnosed celiac disease based on tissue transglutaminase IgA (tTGA) according to age categories. Positive was defined by tTGA ≥ 4 U/mL

Figure 2

Cumulative incidence of clinical diagnosis based on celiac disease serology status. A. Individuals are grouped according to serology result after those with equivocal serology were excluded. The cumulative incidence of clinical diagnosis was significantly higher in individuals with undiagnosed celiac disease compared to controls. B. According to categories of tTG titers (<4, 4–10, or ≥10 U/mL), event rates were significantly higher in individuals with strong tTG positive.

Figure 2

Cumulative incidence of clinical diagnosis based on celiac disease serology status. A. Individuals are grouped according to serology result after those with equivocal serology were excluded. The cumulative incidence of clinical diagnosis was significantly higher in individuals with undiagnosed celiac disease compared to controls. B. According to categories of tTG titers (<4, 4–10, or ≥10 U/mL), event rates were significantly higher in individuals with strong tTG positive.

Figure 3

Cumulative event rate of clinical diagnosis for cohort members according to their age, estimated as a function of their age rather than time after blood draw. A. Individuals are grouped according to serology result after those with equivocal serology were excluded. The cumulative rate of celiac disease diagnosis across age was markedly higher in seropositive persons (p<.001), in whom median age at celiac disease diagnosis was 53.1 years. B. All individuals in the cohort are included and grouped according to tTGA <4 4–10, or ≥10 U/mL, event rates across age were higher for increasing tTGA levels (p<.001), with median age at celiac disease diagnosis of 49.7 years for individuals with tTGA ≥10 U/mL. tTGA=Tissue transglutaminase immunoglobulin A

Figure 4

Kaplan-Meier survival curve for persons with positive and negative serology.