Diagnosis of coeliac disease

doi:10.1016/j.bpg.2005.02.006

Best Practice & Research Clinical Gastroenterology

Volume 19, Issue 3, June 2005, Pages 389-400

https://doi.org/10.1016/j.bpg.2005.02.006 Get rights and content

The diagnosis of coeliac disease depends on the finding of characteristic, though not specific changes, of intraepithelial lymphocytosis, crypt hyperplasia and various degrees of villous height reduction identified in duodenal biopsies of individuals ingesting a gluten containing diet, together with symptomatic and histologic improvement on gluten withdrawal. Serologic testing has become the main mode of determining who will undergo biopsy. The IgA endomysial antibody and IgA tissue transglutaminase antibody have approximately 90% sensitivity and specificity, though there are reports of lower sensitivity and specificity in the clinical practice setting. This is due to lower titers of these antibodies in the presence of lesser degrees of mucosal damage. The widespread availability of serologic tests for coeliac disease allows the diagnosis to be considered by any physician. Gastroenterologists will be required to interpret the results of serologic tests and perform duodenal biopsies when indicated. Pathologists likewise need to be better acquainted with the more subtle changes of cell mediated immunity within the mucosa that are suggestive of underlying gluten sensitivity.

Section snippets

Who should have serologic testing?

The clinical suspicion of coeliac disease may be based on the presence of gastrointestinal symptoms, i.e. those with classical, diarrhea-predominant syptoms with or without a malabsorption syndrome. The next most common group in whom the diagnosis should be considered are those with manifestations of malabsorption of nutrients or vitamins. This includes patients with iron deficiency anemia in the absence of gastrointestinal bleeding, folic acid deficiency, manifestations of calcium or vitamin D

Serology testing

The widespread availability of serologic tests has permitted the diagnosis of coeliac disease to be considered and tested for by any physician. The most sensitive tests are based on the use of IgA isotypes. The available tests include antigliadin antibodies as well as connective tissue antibodies: reticulin, endomysial and tissue transglutaminase antibodies. The lower sensitivity and specificity of the antigliadin antibodies (70–80%) have resulted in their use being called into question for the

Selective IgA deficiency

Selective IgA deficiency (SIgAD) occurs more commonly in patients with coeliac disease than the general population.⁴⁵ As a result, patients with coeliac disease lack IgA-EMA, IgA-tTG and IgA-antigliadin antibodies.46, 47 In order to detect coeliac disease in those with SIgAD a total IgA level should be incorporated into the testing for coeliac disease,⁴⁷ as well as an IgG antibody-based test, either IgG-antigliadin or IgG-tTG.⁴⁸

Seronegative coeliac disease

Several studies have demonstrated that serologic studies may lack sensitivity when used in the practice setting.26, 30, 49, 50 Reliance on EMA as a single test has, in fact, underestimated the prevalence of coeliac disease by at least 20–25%.26, 29, 30, 51 This is mainly due to the inclusion of patients with mild mucosal changes, a situation when patients may not express an EMA.25, 28, 49, 52, 53 A similar situation occurs with tissue transglutaminase, with titers decreasing as the mucosal

Role of HLA DQ2/DQ8 assessment

The HLA DQ2 is found in up to 90–95% of patients with coeliac disease, while most of the remaining patients are HLA DQ8.62, 63 However, these HLA alleles are found in up to 40% of the general population. They appear to be a necessary, but not sufficient, factor in the pathogenesis of coeliac disease. The role of determining whether an individual carries HLA DQ2 or DQ8 in the assessment of coeliac disease lies in their high negative predictive value.⁶⁴ The main roles are in determining whether

Biopsy and histology

Biopsy of the small intestine remains the gold standard in the diagnosis of coeliac disease (Figure 2). Biopsies of the descending duodenum, rather than the more distal intestine seem sufficient for the diagnosis of coeliac disease.65, 66 Due to the patchy nature of villous changes in coeliac disease67, 68, 69 multiple biopsies are necessary, though standard sized forceps are sufficient.⁶⁶

The recognition of the spectrum of histological changes in coeliac disease, as classified by Marsh1, 70 or

Endoscopic Markers of coeliac disease

Multiple endoscopic signs have been described in patients with coeliac disease. They include scalloping of folds,⁸² reduced or absent duodenal folds,⁸³ mucosal fissures or grooves⁸⁴ and visible vascularity of duodenal mucosa.⁸⁵ However, these endoscopic signs are neither particularly sensitive for the diagnosis of coeliac disease,86, 87, 88 nor specific.⁷⁵

Biopsy should be performed if the diagnosis of coeliac disease is considered, irrespective of the visual appearance of the mucosa. In

Other proposed antibody tests for coeliac disease

Antigliadin antibodies, EMA and tTG antibodies are recovered in duodenal secretions and stool of patients with coeliac disease90, 91, 92 as well as normal individuals,90, 91 some of whom may have latent gluten sensitivity in the absence of symptomatic coeliac disease.90, 93 IgA-tTG antibodies are also recovered in saliva of patients with coeliac disease⁹⁴ and have been advocated as a non-invasive screening test for coeliac disease by some investigators,⁹⁴ but not all.⁹⁵ Recently both salivary

Conclusion

The diagnosis of coeliac disease depends on the finding of characteristic small intestinal pathological abnormalities together with clinical or histologic improvement on a gluten-free diet. Lesser degrees of mucosal change must be recognised as reactions to gluten in sensitised individuals and must, therefore, not be ignored or dismissed as ‘non-specific’. EMA and tTG antibodies have high sensitivity and specificity towards celiac disease, though there are some pitfalls in their use, as

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Coeliac disease is a common autoimmune disorder induced by ingesting gluten, the protein component of wheat, barley, and rye. It is estimated that one-in-hundred people worldwide have coeliac disease, of whom the majority remain undiagnosed. Coeliac disease is characterized by a wide range of gastrointestinal and extraintestinal symptoms but can also present asymptomatically. Diagnosing coeliac disease depends on the concordance of clinical, serological and histopathological data. However, the diagnosis can be challenging and frequently overlooked. Undiagnosed coeliac disease is associated with an increased risk of complications and detrimental effects on quality of life. Early diagnosis and treatment of coeliac disease are necessary to reduce the risk of long-term complications.
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Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis.
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These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and management of dermatitis herpetiformis.
These guidelines may support clinicians to improve the diagnosis and management of patients with coeliac disease.
Resolution-based distillation for efficient histology image classification
2021, Artificial Intelligence in Medicine
Developing deep learning models to analyze histology images has been computationally challenging, as the massive size of the images causes excessive strain on all parts of the computing pipeline. This paper proposes a novel deep learning-based methodology for improving the computational efficiency of histology image classification. The proposed approach is robust when used with images that have reduced input resolution, and it can be trained effectively with limited labeled data. Moreover, our approach operates at either the tissue- or slide-level, removing the need for laborious patch-level labeling. Our method uses knowledge distillation to transfer knowledge from a teacher model pre-trained at high resolution to a student model trained on the same images at a considerably lower resolution. Also, to address the lack of large-scale labeled histology image datasets, we perform the knowledge distillation in a self-supervised fashion. We evaluate our approach on three distinct histology image datasets associated with celiac disease, lung adenocarcinoma, and renal cell carcinoma. Our results on these datasets demonstrate that a combination of knowledge distillation and self-supervision allows the student model to approach and, in some cases, surpass the teacher model's classification accuracy while being much more computationally efficient. Additionally, we observe an increase in student classification performance as the size of the unlabeled dataset increases, indicating that there is potential for this method to scale further with additional unlabeled data. Our model outperforms the high-resolution teacher model for celiac disease in accuracy, F1-score, precision, and recall while requiring 4 times fewer computations. For lung adenocarcinoma, our results at 1.25× magnification are within 1.5% of the results for the teacher model at 10× magnification, with a reduction in computational cost by a factor of 64. Our model on renal cell carcinoma at 1.25× magnification performs within 1% of the teacher model at 5× magnification while requiring 16 times fewer computations. Furthermore, our celiac disease outcomes benefit from additional performance scaling with the use of more unlabeled data. In the case of 0.625× magnification, using unlabeled data improves accuracy by 4% over the tissue-level baseline. Therefore, our approach can improve the feasibility of deep learning solutions for digital pathology on standard computational hardware and infrastructures.
Histopathologic aspects of gluten-related disorders
2021, Gluten-Related Disorders: Diagnostic Approaches, Treatment Pathways, and Future Perspectives
Histopathology of gluten-related disorders (GRDs) including celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), nonceliac gluten sensitivity (NCGS), and wheat allergy (WA) is characterized by varying degrees of abnormalities of the small intestinal mucosa resulting from a T-cell-mediated hypersensitivity reaction to wheat and its protein components. In all these conditions, duodenal mucosal pathology may show intraepithelial lymphocytosis or as recently named, “microscopic enteritis” which by no means is specific to gluten-related damage. The morphologic continuum of CD involves a spectrum of abnormalities including intraepithelial lymphocytosis, crypt hyperplasia, and completely flat mucosa. In NCGS villous architecture is usually maintained with only mild or no increase in intraepithelial lymphocytes (IELs). The histopathology of WA is yet to be described, although, microscopic enteropathy with increased eosinophils and IELs may occur in the context of WA. The limitations of histopathologic evaluation make clinical information an essential component of the diagnosis of GRDs, which requires close clinicopathologic collaboration.
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La enfermedad celiaca es una enteropatía crónica mediada por el sistema inmune e inducida por la exposición al gluten en individuos genéticamente predispuestos. Tiene una prevalencia aproximada del 1%, con un aumento de incidencia en las últimas décadas. Descrita clásicamente como una enfermedad de la infancia, cada vez es más frecuente su diagnóstico en la edad adulta, con formas menos sintomáticas, con síntomas digestivos inespecíficos y manifestaciones extraintestinales. El diagnóstico en el adulto se basa en la presencia de clínica compatible, la demostración de enteropatía en las biopsias duodenales y la presencia de serología positiva; siendo de especial utilidad el estudio genético en aquellos casos en los que existe discordancia de estos factores y para el cribado en familiares de primer grado y enfermedades asociadas. El tratamiento consiste en mantener una dieta sin gluten de por vida, con un seguimiento posterior para evaluar el cumplimiento dietético y valorar la evolución clínica, de cara detectar de forma precoz complicaciones, enfermedades asociadas y alteraciones nutricionales.
Celiac disease. Celiac disease is a chronic, immune-mediated enteropathy, caused by gluten exposure in genetically predisposed individuals. Its prevalence is estimated in 1% and has been growing in the last decades. Originally described as a childhood disease, nowadays it is frequently diagnosed in adults, often with less symptomatic forms, involving mild digestive symptoms and extra intestinal manifestations. Celiac disease diagnosis in adult individuals must be based on compatible clinical data, proof of enteropathy in duodenal biopsy samples, and positive serology. Genetic testing is specially useful in those cases were the results of prior tests are discordant and for screening in first-degree relatives and in patients with associated diseases. The mainstay of treatment is maintaining a lifelong gluten-free diet, with subsequent follow-up to evaluate adherence and clinical evolution in order to monitor nutritional status and achieve early detection of complications and associated diseases.
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Context: Celiac disease (CD) prevalence and diagnosis have increased substantially in recent years. The current gold standard for CD confirmation is visual examination of duodenal mucosal biopsies. An accurate computer-aided biopsy analysis system using deep learning can help pathologists diagnose CD more efficiently. Subjects and Methods: In this study, we trained a deep learning model to detect CD on duodenal biopsy images. Our model uses a state-of-the-art residual convolutional neural network to evaluate patches of duodenal tissue and then aggregates those predictions for whole-slide classification. We tested the model on an independent set of 212 images and evaluated its classification results against reference standards established by pathologists. Results: Our model identified CD, normal tissue, and nonspecific duodenitis with accuracies of 95.3%, 91.0%, and 89.2%, respectively. The area under the receiver operating characteristic curve was >0.95 for all classes. Conclusions: We have developed an automated biopsy analysis system that achieves high performance in detecting CD on biopsy slides. Our system can highlight areas of interest and provide preliminary classification of duodenal biopsies before review by pathologists. This technology has great potential for improving the accuracy and efficiency of CD diagnosis.

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7Diagnosis of coeliac disease

Section snippets

Who should have serologic testing?

Serology testing

Selective IgA deficiency

Seronegative coeliac disease

Role of HLA DQ2/DQ8 assessment

Biopsy and histology

Endoscopic Markers of coeliac disease

Other proposed antibody tests for coeliac disease

Conclusion

Gastroenterology

Lancet

Gastroenterology

Lancet

Am J Gastroenterol

Am J Gastroenterol

Lancet

Gastroenterology

Gastroenterology

Am J Gastroenterol

J Pediatr

Am J Gastroenterol

Am J Gastroenterol

Neth J Med

Clin Gastroenterol Hepatol

Am J Gastroenterol

Gastrointest Endosc

Gastrointest Endosc

Am J Gastroenterol

Am J Gastroenterol

Gastrointest Endosc

Gastrointest Endosc

Lancet

Gastroenterology

Pathol Res Pract

Gastroenterology

Gastroenterology

Gastrointest Endosc

Gastrointest Endosc

Am J Gastroenterol

Gastrointest Endosc

Am J Gastroenterol

Gastrointest Endosc

Gastroenterology

Am J Gastroenterol

Gastroenterology

J Pediatr

Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition

Arch Dis Child

Chronic unexplained hypertransaminasemia may be caused by occult celiac disease

Hepatology

Autoimmune thyroid diseases and coeliac disease

Eur J Gastroenterol Hepatol

High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus

Am J Gastroenterol

Celiac disease in an adult population with insulin-dependent diabetes mellitus: use of endomysial antibody testing

Am J Gastroenterol

Autoantibodies to tissue transglutaminase in Sjogren's syndrome and related rheumatic diseases

J Rheumatol

High prevalence of celiac sprue among patients with primary biliary cirrhosis

J Clin Gastroenterol

Celiac neuropathy

Neurology

Coeliac disease, epilepsy, and cerebral calcifications. The Italian Working Group on Coeliac Disease and Epilepsy

Lancet

Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features

J Neurol Neurosurg Psychiatry

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study

Arch Intern Med

7
Diagnosis of coeliac disease