Morbidity and Mortality Among Older Individuals With Undiagnosed Celiac Disease

doi:10.1053/j.gastro.2010.05.041

Gastroenterology

Volume 139, Issue 3, September 2010, Pages 763-769

https://doi.org/10.1053/j.gastro.2010.05.041 Get rights and content

Background & Aims

Outcomes of undiagnosed celiac disease (CD) are unclear. We evaluated the morbidity and mortality of undiagnosed CD in a population-based sample of individuals 50 years of age and older.

Methods

Stored sera from a population-based sample of 16,886 Olmsted County, Minnesota, residents 50 years of age and older were tested for CD based on analysis of tissue transglutaminase and endomysial antibodies. A nested case-control study compared serologically defined subjects with CD with age- and sex-matched, seronegative controls. Medical records were reviewed for comorbid conditions.

Results

We identified 129 (0.8%) subjects with undiagnosed CD in a cohort of 16,847 older adults. A total of 127 undiagnosed cases (49% men; median age, 63.0 y) and 254 matched controls were included in a systematic evaluation for more than 100 potentially coexisting conditions. Subjects with undiagnosed CD had increased rates of osteoporosis and hypothyroidism, as well as lower body mass index and levels of cholesterol and ferritin. Overall survival was not associated with CD status. During a median follow-up period of 10.3 years after serum samples were collected, 20 cases but no controls were diagnosed with CD (15.2% Kaplan–Meier estimate at 10 years).

Conclusions

With the exception of reduced bone health, older adults with undiagnosed CD had limited comorbidity and no increase in mortality compared with controls. Some subjects were diagnosed with CD within a decade of serum collection, indicating that although most cases of undiagnosed CD are clinically silent, some result in symptoms. Undiagnosed CD can confer benefits and liabilities to older individuals.

Section snippets

Setting

Population-based epidemiologic research can be conducted in Olmsted County (2000 population, ∼124,000) because medical care is virtually self-contained within the community and there are relatively few providers.³⁴ The 2 major medical care providers (Mayo Clinic and Olmsted Medical Center) each use a dossier (or unit record) system whereby all medical information for each individual is accumulated in a single life-long record. These clinical data are accessible because Mayo Clinic has

Results

Among subjects whose disease status was unknown, 16,886 Olmsted County, Minnesota, residents age 50 and older who had consented to use of their serum for research were screened for CD. In total, 163 (1.0%) individuals tested positive for tTGA and underwent confirmatory EMA testing, whereas 143 had borderline tTGA levels (2.0–4.0 U/mL) and also were EMA tested. Based on a combined serology status of both the tTGA and EMA result, 39 subjects were considered equivocal and were excluded from

Discussion

Among the principal findings of this study, undiagnosed CD was found to be associated with impaired bone health including an increased rate of osteoporosis and lower bone density scores, but was not associated with increased mortality or the majority of comorbidities and symptoms commonly linked to diagnosed CD.

As found in our study, undiagnosed CD in older adults was not associated with an increased risk of mortality, data that are consistent with a recent study from Europe.³³ This is in

References (43)

G. Corrao et al.
Mortality in patients with coeliac disease and their relatives: a cohort study
Lancet
(2001)
P.H. Green et al.
Risk of malignancy in patients with celiac disease
Am J Med
(2003)
M. Viljamaa et al.
Malignancies and mortality in patients with coeliac disease and dermatitis herpetiformis: 30-year population-based study
Dig Liver Dis
(2006)
J.A. Murray et al.
Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease
Am J Clin Nutr
(2004)
A. Vilppula et al.
Undetected coeliac disease in the elderly: a biopsy-proven population-based study
Dig Liver Dis
(2008)
W. Dieterich et al.
Autoantibodies to tissue transglutaminase as predictors of celiac disease
Gastroenterology
(1998)
S. Sulkanen et al.
Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease
Gastroenterology
(1998)
W. Dieterich et al.
Antibodies to tissue transglutaminase as serologic markers in patients with dermatitis herpetiformis
J Invest Dermatol
(1999)
J.C. Gomez et al.
Value of a screening algorithm for celiac disease using tissue transglutaminase antibodies as first level in a population-based study
Am J Gastroenterol
(2002)
G. Bottaro et al.
The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases
Am J Gastroenterol
(1999)

A. Rubio-Tapia et al.

Increased prevalence and mortality in undiagnosed celiac disease

Gastroenterology

(2009)

L.J. Melton

History of the Rochester Epidemiology Project

Mayo Clin Proc

(1996)

J.A. Murray et al.

Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001

Clin Gastroenterol Hepatol

(2003)

P. Collin

Should adults be screened for celiac disease?What are the benefits and harms of screening?

Gastroenterology

(2005)

M.L. Mearin et al.

Coeliac disease: is it time for mass screening?

Best Pract Res Clin Gastroenterol

(2005)

E. Fabiani et al.

Compliance with gluten-free diet in adolescents with screening-detected celiac disease: a 5-year follow-up study

J Pediatr

(2000)

H.B. Cook et al.

Adult coeliac disease: prevalence and clinical significance

J Gastroenterol Hepatol

(2000)

J. West et al.

Seroprevalence, correlates, and characteristics of undetected coeliac disease in England

Gut

(2003)

S. Lohi et al.

Increasing prevalence of coeliac disease over time

Aliment Pharmacol Ther

(2007)

J. West et al.

Malignancy and mortality in people with coeliac disease: population based cohort study

BMJ

(2004)

M. Solaymani-Dodaran et al.

Long-term mortality in people with celiac disease diagnosed in childhood compared with adulthood: a population-based cohort study

Am J Gastroenterol

(2007)

Cited by (135)

Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis
2024, Value in Health
Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use.
A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research.
Using serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children.
For adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.
Mortality and causes of death in different celiac disease phenotypes during long-term follow-up
2022, Digestive and Liver Disease
Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce.
To determine long-term mortality in celiac disease.
The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 – 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time.
During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85–1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38–4.24 and HR 2.14, 95% CI 1.05–4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09–1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality
Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.
Celiac Disease in Children
2021, Pediatric Clinics of North America
Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?
2021, Medical Hypotheses
Thyroid nodules are among highly prevalent thyroid diseases. To make a distinction between benign and malignant thyroid nodules are of cumbersome significance for each endocrinologist. There is no unique and completely accurate diagnostic test, method, or even biomarker that points to a malignant thyroid nodule. Many studies in modern thyroidology are conducted to determine the usefulness of individual biomarkers, which could help clinicians detect thyroid nodules' potential malignant nature. One interesting biomarker with a promising diagnostic potential for the thyroid gland pathological conditions is nitric oxide (NO). Inducible nitric oxide synthase expression is increased in thyroiditis cases and even more in thyroid carcinoma cases, directly connected with increased NO levels in both pathological conditions. We hypothesize that the basal levels of nitrite/nitrate in serum and biopsy washout could indicate nodules' malignant nature.
Epidemiology, Presentation, and Diagnosis of Celiac Disease
2021, Gastroenterology
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten–HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
Measurement of Forearm Bone Density by Dual Energy X-Ray Absorptiometry Increases the Prevalence of Osteoporosis in Men With Celiac Disease
2020, Clinical Gastroenterology and Hepatology
Guidelines advise measurement of bone mineral density (BMD) in patients with a diagnosis of celiac disease. The lumbar spine (LS) and hip sites are usually measured. Although skeletal sites rich in trabecular bone are believed to be vulnerable to osteoporosis in patients with celiac disease, most studies have not measured the cortical distal 1/3-radius.
We collected data from 721 patients (mean age, 43.6 years; 68.4% female) with celiac disease who underwent 3-site dual energy x-ray absorptiometry (DXA, at a median 1.22 years after diagnosis). We assessed skeletal site- and sex-specific osteoporosis prevalence and the incremental utility of 1/3-radius measurement by DXA.
Mean T- and Z-scores were normal in patients, but 43.3% had osteopenia and 19.6% had osteoporosis. Osteoporosis was found in 12.1% of patients at the LS, 5.3% of patients at the total hip, 7.6% of patients at the femoral neck, and 11.5% of patients at the 1/3-radius. A greater degree of villous atrophy at diagnosis was associated with male sex and lower T-scores at the 1/3-radius (P = .03), but not other skeletal sites. Isolated forearm osteoporosis was detected in 4.9% of patients. A higher proportion of patients with isolated forearm osteoporosis were male and had a greater weight and body mass index (all P < .01, compared to patients with osteoporosis only at other sites). Z-scores were lower at the LS and 1/3-radius and osteoporosis was more common in men than women. In men, the 1/3-radius was the most frequent site for osteoporosis. Among patients 50 years or older, isolated forearm osteoporosis was present in 10.7%.
Based on DXA analysis of patients with celiac disease, the prevalence of osteoporosis appears to be underestimated—particularly in men when BMD at the 1/3-radius is not measured. Degree of villous atrophy is associated with BMD at the 1/3-radius and nearly 5% of patients have osteoporosis limited to that site. Recommendations for osteoporosis screening in patients with celiac disease should include measurement of the distal 1/3-radius in addition to the hip and LS.

View all citing articles on Scopus

: Conflicts of interest The authors disclose no conflicts.

: Funding This work was supported by research grants R01-DK57892, P01 CA62242, R01-AR30582, and T-32 AI07047 (A.R.-T.) from the National Institutes of Health, U.S. Public Health Service. The project described was supported by grant number 1 UL1 RR024150 from the National Center for Research Resources, a component of the National Institutes of Health, and the National Institutes of Health Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the National Institutes of Health. Information on the National Center for Research Resources is available at http://www.ncrr.nih.gov/. Information on Reengineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov.

View full text

Clinical—Alimentary TractMorbidity and Mortality Among Older Individuals With Undiagnosed Celiac Disease

Background & Aims

Methods

Results

Conclusions

Section snippets

Setting

Results

Discussion

Lancet

Am J Med

Dig Liver Dis

Am J Clin Nutr

Dig Liver Dis

Gastroenterology

Gastroenterology

J Invest Dermatol

Am J Gastroenterol

Am J Gastroenterol

Gastroenterology

Mayo Clin Proc

Clin Gastroenterol Hepatol

Gastroenterology

Best Pract Res Clin Gastroenterol

J Pediatr

Adult coeliac disease: prevalence and clinical significance

J Gastroenterol Hepatol

Seroprevalence, correlates, and characteristics of undetected coeliac disease in England

Gut

Increasing prevalence of coeliac disease over time

Aliment Pharmacol Ther

Malignancy and mortality in people with coeliac disease: population based cohort study

BMJ

Long-term mortality in people with celiac disease diagnosed in childhood compared with adulthood: a population-based cohort study

Am J Gastroenterol

Clinical—Alimentary Tract
Morbidity and Mortality Among Older Individuals With Undiagnosed Celiac Disease