Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities.

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10×ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×-5.1× in the clinical cohort and 1.3×-4.9× in the family cohort, respectively. Using the assays' own cut-offs (1×ULN) the PPVs ranged 84-100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10×ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower.

Diagnosing Celiac Disease: Towards Wide-Scale Screening and Serology-Based Criteria?

Celiac disease is one of the most common food-related chronic disorders in children. Unfortunately, this multifaceted disease is challenging to recognize and remains markedly underdiagnosed. Screening of either known at-risk groups or even the whole population could increase the suboptimal diagnostic yield substantially. Many recent guidelines recommend screening of at least selected risk groups, but more wide-scale screening remains controversial. The increasing prevalence of celiac disease and the development of autoantibody assays have also led to a gradual shift in the diagnostics towards less invasive serology-based criteria in a subgroup of symptomatic children. The main open questions concern whether these criteria are applicable to all countries and clinical settings, as well as to adult patients. On the other hand, widening screening and the mistaken practice of initiating a gluten-free diet before the appropriate exclusion of celiac disease increase the number of borderline seropositive cases, which may also challenge the classical histopathological diagnostics. Sophisticated diagnostic methods and a deeper understanding of the natural history of early developing celiac disease may prove useful in these circumstances.

Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities.

BACKGROUND: The revised paediatric criteria for coeliac disease allow omission of duodenal biopsies in symptomatic children who have specific serology and coeliac disease-associated genetics. It remains unclear whether this approach is also applicable for adults with various clinical presentations. AIM: To evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for coeliac disease. METHODS: Three study cohorts comprised adults with high-risk clinical coeliac disease suspicion (n = 421), moderate-risk family members of coeliac disease patients (n = 2357), and low-risk subjects from the general population (n = 2722). Serological and clinical data were collected, and "triple criteria" for coeliac disease comprised transglutaminase 2 antibodies >10× the upper limit of normal, positive endomysium antibodies, and appropriate genetics without requirement of symptoms. The diagnosis was based on intestinal biopsy. RESULTS: The diagnosis of coeliac disease was established in 274 subjects. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria". All had histologically proven coeliac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 (33%) of all 274 newly diagnosed patients could have avoided biopsy, including 37% among high-risk, 20% among moderate-risk, and 48% among low-risk patients. No histological findings other than coeliac disease were found in the biopsies of "triple positive" subjects. CONCLUSIONS: Coeliac disease can reliably and safely be diagnosed without biopsy in adults fulfilling the "triple criteria" regardless of the pre-test probability. Revised criteria would enable the number of endoscopies to be reduced by one-third.

Delayed celiac disease diagnosis predisposes to reduced quality of life and incremental use of health care services and medicines: A prospective nationwide study.

BACKGROUND: Celiac disease is challenging to recognize, predisposing to long diagnostic delay. Currently, associated factors and significance of the delay remain obscure. OBJECTIVE: The objective of this article is to investigate associated sociodemographic risk factors and health consequences of diagnostic delay in celiac disease. METHODS: Altogether 611 patients were surveyed at diagnosis and after one year on a gluten-free diet regarding sociodemographic variables, well-being and use of medicines and health care services. Quality of life was measured by a validated Psychological General Well-Being (PGWB) questionnaire. The results were compared between patients with and without delayed (≥3 years) diagnosis. RESULTS: A total of 332 (54%) individuals reported a delay of ≥3 years. Associated with the delay were being a student or homemaker, but not gender, marital or occupational status, site of diagnosis or place of residence. Patients with the delay also had decreased self-perceived health and poorer PGWB scores compared to those without delay; in anxiety and general health this was seen even on a gluten-free diet. Days of sickness and doctor visits as well as use of drugs for dyspepsia and antidepressants were increased in the delay group both before and after diagnosis. CONCLUSION: A delay in celiac disease diagnosis predisposes to reduced well-being and incremental use of medicines and health care services, both before diagnosis and one year after diagnosis.

Factors associated with long diagnostic delay in celiac disease.

OBJECTIVE: Here, we investigated the factors associated with long diagnostic delay in celiac disease and the impact of the national Current Care Guidelines in reducing the delay. MATERIAL AND METHODS: This population-based study involved 825 adult celiac disease patients. The diagnosis was considered delayed when the interval between first symptoms and diagnosis was >10 years. The patients were asked about the duration and type of symptoms before diagnosis, time and site (tertiary, secondary, or primary care) of the diagnosis, family history of the disease, and presence of significant comorbidities. Analysis was performed by binary logistic regression. RESULTS: Altogether, 261 (32%) out of 825 participants reported a diagnostic delay of >10 years. Female gender, neurological or musculoskeletal disorders and presence of diarrhea, abdominal pain, and malabsorption were associated with prolonged delay. Male gender, diagnosis after the introduction of the first Current Care Guidelines in 1997, and being detected by serological screening, and family history of celiac disease were associated with a lower risk of delayed diagnosis. Factors not associated with the delay were site of diagnosis, age, and presence of dermatitis herpetiformis, type 1 diabetes, or thyroidal disease. CONCLUSION: The number of long diagnostic delays in celiac disease has decreased over the past decades. The shift of diagnostics from secondary and tertiary care to primary care has not been detrimental. National guidelines together with increased awareness and active screening in at-risk groups of celiac disease are important in these circumstances.