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Sareila H, Kurppa K, Huhtala H, Laurikka P, Arnala S, Koskela T, Kaukinen K, Kivelä L. Patient perceptions of the Finnish guidelines enabling coeliac disease diagnosis without biopsies in adults. Scand J Gastroenterol 2025; 60:20-27. [PMID: 39620385 DOI: 10.1080/00365521.2024.2431628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/09/2024] [Accepted: 11/11/2024] [Indexed: 04/05/2025]
Abstract
OBJECTIVES Diagnosis of coeliac disease based on serology only has been allowed since 2018 in Finland for adults meeting specific criteria. We studied the patient experiences and perceptions of this novel diagnostic option. METHODS Altogether 194 adult patients were questioned on socio-demographic and health-related characteristics, quality of life and various coeliac disease-related issues. The results were compared between patients diagnosed with intestinal biopsy or based on serology only. RESULTS Altogether 69 (36%) of the patients were diagnosed without duodenal biopsies. They were younger (median 43 vs. 51 years, p = 0.046), diagnosed more recently (2021 vs. 2020, p < 0.001) and more often in primary health care (78% vs. 43%, p = 0.001), had fewer esophageal symptoms at diagnosis (17% vs. 30%, p = 0.046) and considered the diagnostic process easier (49% vs. 30%, p = 0.032) than those diagnosed by duodenal biopsy (n = 125). The no-biopsy group received less often dietician follow-up (4% vs. 17%, p = 0.012), reported more persistent symptoms (36% vs. 21%, p = 0.026) and experienced more stress due to the diet (68% vs. 47%, p = 0.039). Symptom persistence or stress were not associated with year of diagnosis or dietician follow-up. The groups were comparable in socio-economic characteristics, general health, quality of life, diagnostic delay, dietician guidance at diagnosis, and dietary adherence. CONCLUSIONS The non-invasive approach resulted in de-centralized diagnosis and easier patient-experienced diagnostic process of coeliac disease, but was associated with increased risk for persistent symptoms and stress due to gluten-free diet. These results highlight the significance of appropriate patient guidance and support regardless of the diagnostic strategy.
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Affiliation(s)
- Hanna Sareila
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Hatanpää Health Care Centre, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University, Tampere, Finland
- Department of Paediatrics, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
- The University Consortium of Seinäjoki, Seinäjoki, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Pilvi Laurikka
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Kanta-Häme Central Hospital, Wellbeing Services County of Hanta-Häme, Hämeenlinna, Finland
| | - Sanna Arnala
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Tuomas Koskela
- Department of General Practice, Faculty of Medicine and Health Technology, University of Tampere, Finland
- Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Laura Kivelä
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Paediatrics, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
- Children's Hospital, Helsinki University Hospital, Helsinki, Finland
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Katunin E, Aitokari L, Kivelä L, Ilus T, Huhtala H, Kaukinen K, Kurppa K. Measured levels of positive transglutaminase 2 antibodies are not associated with presentation or incidental endoscopic findings at celiac disease diagnosis. Scand J Gastroenterol 2024; 59:419-424. [PMID: 38164975 DOI: 10.1080/00365521.2023.2298709] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVES It has been suggested that celiac disease could be diagnosed non-invasively in adults with transglutaminase antibody (TGA) levels >10x upper limit of normal (ULN). It is, however, unclear if high values signify more advanced disease and higher risk of co-morbidities. We investigated the association between the TGA levels, clinical characteristics and non-celiac endoscopic findings. METHODS Medical data on 450 celiac disease patients at diagnosis were collected. They were further divided into those with high positive (>10x ULN, n = 164), moderately positive (1-10x ULN, n = 219), and negative (n = 67) TGA. RESULTS Median age of patients was 50 years and 60% were women. Patients with negative TGA were older (median age 58 vs. 51 vs. 46 years respectively, p = 0.002) and had more often weight loss (27% vs. 10% vs. 9%, p < 0.001) and abdominal pain or dyspepsia (40% vs 27% vs. 22%, p = 0.017) than did those with moderately positive/high TGA. The groups did not differ in sex, BMI, or other symptoms. Major endoscopic findings included one esophageal adenocarcinoma presenting with dysphagia, six esophagitis, three gastric ulcers, and 39 H. Pylori or other active gastritis. High, moderately positive or negative TGA levels were not associated with these findings in crude or age-adjusted analyses. CONCLUSIONS Presentation was similar in patients with moderate or high levels of TGA, whereas patients with negative TGA were different. The level of TGA was not associated with incidental endoscopic findings and the only malignancy presented with an alarm symptom atypical to celiac disease.
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Affiliation(s)
- Eneli Katunin
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Department of Internal Medicine, Kanta-Häme Central Hospital, Hämeenlinna, Finland
| | - Linnea Aitokari
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Laura Kivelä
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
- University of Helsinki and Helsinki University Hospital, Children's Hospital, and Pediatric Research Center, Helsinki, Finland
- Pediatric Research Institute, University of Oslo, Norway
| | - Tuire Ilus
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
- The University Consortium of Seinäjoki, Seinäjoki, Finland
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Qureshi MH. The Correlation Between Serum Anti-tissue Transglutaminase (Anti-tTG) Antibody Levels and Histological Severity of Celiac Disease in Adolescents and Adults: A Meta-Analysis. Cureus 2023; 15:e51169. [PMID: 38283435 PMCID: PMC10814693 DOI: 10.7759/cureus.51169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2023] [Indexed: 01/30/2024] Open
Abstract
Celiac disease is an autoimmune disorder characterized by a broad spectrum of histological damage to the intestinal mucosa. Comprehension and understanding of the association between anti-tissue transglutaminase (anti-tTG) antibody levels and the histological severity of celiac disease are not well established, prompting the need for meta-analysis. This study aims to offer insights into the diagnostic abilities of anti-tTG antibody levels in determining the histological severity of celiac disease by providing quantitative evidence based on a diverse range of studies. An extensive search was conducted across four electronic research databases to identify primary research articles reporting serum anti-tTG antibody levels in correlation with different Marsh grades, signifying the histological severity of celiac disease. The software tool RevMan 5.4 (the Cochrane Collaboration, London, UK) was used to compile standardized mean differences (SMD) alongside their respective confidence intervals. A total of 13 studies were included in the meta-analysis, with a patient pool of 2505 patients. Marsh grade I and II were found to have higher anti-tTG antibody levels compared to those with grade 0 (SMD 1.50; 95% CI: 1.12, 1.87; p-value <0.00001). Antibody levels were higher in Marsh grade IIIa when compared to both grade 0 (SMD 0.97; 95% CI: 0.67, 1.28; p-value <0.00001) and grade ≤2 (SMD 0.61; 95% CI: 0.44, 0.79; p-value <0.00001). Patients with Marsh IIIb also reported greater anti-tTG levels compared to grade 0 (SMD 1.48; 95% CI: 0.99, 1.96; p-value <0.00001) and grade ≤2 (SMD 0.98; 95% CI: 0.79, 1.18; p-value <0.00001). Likewise, Marsh grade ≥IIIc reported high levels of anti-tTG antibodies in comparison with grade 0 (SMD 1.06; 95% CI: 0.72, 1.39; p-value <0.00001) and grade ≤2 (SMD 1.18; 95% CI: 1.02, 1.34; p-value <0.00001). Our meta-analysis revealed a consistent, robust correlation between anti-tTG antibody levels and the histological severity of celiac disease, with a clear trend of increasing antibody levels corresponding to the severity of mucosal damage. Large-scale primary research initiatives are needed to reach definitive conclusions.
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Affiliation(s)
- Muhammad Hassan Qureshi
- Medicine, Combined Military Hospital, Lahore, PAK
- Health, Medicine, and Social Care, Anglia Ruskin University, Cambridge, GBR
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Novis CL, Wahl E, Camacho E, Aure MA, Mahler M, Nandakumar V. Performance Assessment of a Novel Multianalyte Methodology for Celiac Disease Biomarker Detection and Evaluation of the Serology-Alone Criteria for Biopsy-Free Diagnosis. Arch Pathol Lab Med 2023; 147:1422-1430. [PMID: 36856668 DOI: 10.5858/arpa.2022-0385-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2022] [Indexed: 03/02/2023]
Abstract
CONTEXT.— Serology plays a vital role in celiac disease (CD) diagnosis, and the latest European guidelines advocate for biopsy-free diagnoses in patients with ≥10× the upper limit of normal (ULN) of anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibodies. OBJECTIVE.— To assess performance characteristics of a novel automated particle-based multianalyte technology (Aptiva) for anti-tTG and anti-deamidated gliadin peptide (DGP) antibody detection as compared to the traditional enzyme-linked immunosorbent assay (QUANTA Lite). Performance characteristics of the ≥10× ULN anti-tTG IgA criteria for serologic diagnosis of CD were also evaluated. DESIGN.— Sera samples from 703 patients were tested for anti-tTG IgA, anti-tTG immunoglobulin G (IgG), anti-DGP IgA, and anti-DGP IgG antibodies on both platforms. In total, 127 patients had medical information and were classified as CD-positive (n = 58) and CD-negative (n = 69) based on biopsy results. Clinical performance characteristics were evaluated. RESULTS.— Anti-tTG IgA detection showed equal clinical sensitivity and specificity of 91% sensitivity and 99% specificity on both platforms. Anti-tTG IgG resulted in moderate sensitivity of 69% and 72%, but high specificity of 100% and 94% on Aptiva and QUANTA Lite, respectively. Anti-DGP IgG displayed comparable sensitivity of 90% and 81%, and a specificity of 94% and 99%, on Aptiva and QUANTA Lite, respectively. Anti-DGP IgA demonstrated greater sensitivity on QUANTA Lite (83%) than Aptiva (69%) and similar specificities of 97% and 98% on QUANTA Lite and Aptiva, respectively. At ≥10× ULN levels for anti-tTG IgA, Aptiva displayed a sensitivity of 72% and a specificity of 100%, and QUANTA Lite showed a sensitivity of 69% and a specificity of 100%. CONCLUSIONS.— Aptiva is a reliable method to measure CD biomarkers with reduced hands-on necessity and high-throughput capabilities. This study supports the use of a ≥10× ULN anti-tTG IgA biopsy-free approach for serologic diagnosis of CD.
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Affiliation(s)
- Camille Leite Novis
- From the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah (Novis, Nandakumar)
| | - Edward Wahl
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Eric Camacho
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Mary Ann Aure
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Michael Mahler
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Vijayalakshmi Nandakumar
- From the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah (Novis, Nandakumar)
- The Department of Pathology, University of Utah School of Medicine, Salt Lake City (Nandakumar)
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Ciacci C, Bai JC, Holmes G, Al-Toma A, Biagi F, Carroccio A, Ciccocioppo R, Di Sabatino A, Gingold-Belfer R, Jinga M, Makharia G, Niveloni S, Norman GL, Rostami K, Sanders DS, Smecuol E, Villanacci V, Vivas S, Zingone F. Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study. Lancet Gastroenterol Hepatol 2023; 8:1005-1014. [PMID: 37696284 DOI: 10.1016/s2468-1253(23)00205-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 06/30/2023] [Accepted: 06/30/2023] [Indexed: 09/13/2023]
Abstract
BACKGROUND Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease. METHODS In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data. FINDINGS We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet. INTERPRETATION Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA. FUNDING None.
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Affiliation(s)
- Carolina Ciacci
- Centre for Coeliac Disease, AOU San Giovanni Di Dio e Ruggi d'Aragona, Salerno, Italy; Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy.
| | - Julio Cesar Bai
- Research Institutes, Universidad del Salvador, Buenos Aires, Argentina; Small Bowel Section, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
| | - Geoffrey Holmes
- Department of Gastroenterology, Royal Derby Hospital, Derby, UK
| | - Abdulbaqi Al-Toma
- Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands
| | - Federico Biagi
- Department of Internal Medicine and Medical Therapy, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy; Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy
| | - Antonio Carroccio
- Unit of Internal Medicine, Cervello Hospital, University of Palermo, Palermo, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, AOUI Policlinico GB Rossi, University of Verona, Verona, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapy, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Rachel Gingold-Belfer
- Gastroenterology Division, Rabin Medical Centre, Beilinson Hospital, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mariana Jinga
- Gastroenterology Department, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, Bucharest, Romania
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sonia Niveloni
- Small Bowel Section, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
| | - Gary L Norman
- Research and Development, Headquarters and Technology Centre for Autoimmunity, Werfen, San Diego, CA, USA
| | - Kamran Rostami
- Gastroenterology Unit, MidCentral DHB, Palmerston North, New Zealand
| | - David S Sanders
- Academic Unit of Gastroenterology, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK
| | - Edgardo Smecuol
- Small Bowel Section, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
| | - Vincenzo Villanacci
- Institute of Pathology, Spedali Civili University of Brescia, Brescia, Italy
| | - Santiago Vivas
- Gastroenterology Unit, University Hospital of Leon, Leon, Spain
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Ventura I, Rodriguez B, Suescum S, Revert F, Revert-Ros F, Moreno MA, Prieto-Ruiz JA, Pérez-Bermejo M. More Than Three Years for Normalisation of Routine Laboratory Values after Gluten Withdrawal in Paediatric Coeliac Patients. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1580. [PMID: 37761542 PMCID: PMC10529408 DOI: 10.3390/children10091580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 09/18/2023] [Accepted: 09/20/2023] [Indexed: 09/29/2023]
Abstract
The assessment of the nutritional and inflammatory status of paediatric patients with coeliac disease is an interesting approach to early diagnosis and functional follow-up. Most authors agree that the normalisation of symptoms takes about one year. The aim of the study was to evaluate the clinical manifestation and normalisation of routine analytics in Spanish children diagnosed with celiac disease. METHODS We performed a retrospective case-control study in Spanish paediatric patients, including 21 celiac patients and 20 healthy controls. The 21 patients selected in the case-control study were followed for 5 years after starting a gluten-free diet (GFD). All patients had type 3 villous atrophy according to the Marsh-Oberhuber classification. A total of 39 blood samples were taken before the start of the GFD, and 109 were taken after. Twenty control sera from healthy donors were used for comparison. RESULTS We found that patients had a subclinical but statistically significant increase in blood calcium, transaminases, and white blood cells, and a decrease in serum iron, at the time of diagnosis. Our study also shows that analytical values normalise within five years on a gluten-free diet. CONCLUSIONS The use of a combination of subclinical changes, including low iron, high calcium, elevated leukocytes, lymphocytes, and ALT levels in blood samples, together with a low growth percentile, is pertinent in detecting coeliac disease. This set of parameters could help in the diagnosis of patients without clinical symptoms. We can also show that the levels of Fe, Ca, transaminases, and leucocytes remain subclinically altered after 3 years, despite the gluten-free diet.
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Affiliation(s)
- Ignacio Ventura
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
- Translational Research Center “San Alberto Magno” CITSAM, Universidad Católica de Valencia ‘San Vicente Mártir’, 46001 Valencia, Spain
| | - Belén Rodriguez
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
| | - Sandra Suescum
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
| | - Fernando Revert
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
- Translational Research Center “San Alberto Magno” CITSAM, Universidad Católica de Valencia ‘San Vicente Mártir’, 46001 Valencia, Spain
| | - Francisco Revert-Ros
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
- Translational Research Center “San Alberto Magno” CITSAM, Universidad Católica de Valencia ‘San Vicente Mártir’, 46001 Valencia, Spain
| | - María Antonia Moreno
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
- Department of Pediatrics, Manises Hospital, 46940 Manises, Spain
| | - Jesús A. Prieto-Ruiz
- Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Universidad Católica de Valencia ‘San Vicent Mártir’, 46001 Valencia, Spain; (I.V.); (B.R.); (S.S.); (F.R.); (F.R.-R.); (M.A.M.); (J.A.P.-R.)
- Translational Research Center “San Alberto Magno” CITSAM, Universidad Católica de Valencia ‘San Vicente Mártir’, 46001 Valencia, Spain
| | - Marcelino Pérez-Bermejo
- SONEV Research Group, Faculty of Medicine and Health Sciences, Catholic University of Valencia, 46001 Valencia, Spain
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Is There a Need to Undertake Conventional Gastroscopy and Biopsy When Making the Diagnosis of Coeliac Disease in Adults? J Clin Gastroenterol 2023; 57:139-142. [PMID: 36598805 DOI: 10.1097/mcg.0000000000001806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Celiac disease is a common autoimmune condition characterized by small intestinal inflammation and mucosal damage triggered by an inappropriate immune response to ingested gluten. Gastroscopy and duodenal biopsy are currently the gold standard approach to diagnosing celiac disease in adults. However, the emergence of highly accurate serological tests for celiac disease in the last 2 decades led to a change in the pediatric guidelines to diagnose celiac disease without biopsy in selected patients. Adopting this no-biopsy approach to diagnose celiac disease in adults remains controversial, but the evidence supporting it is growing.
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8
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Stefanolo JP, Zingone F, Gizzi C, Marsilio I, Espinet ML, Smecuol EG, Khaouli M, Moreno ML, Pinto-Sánchez MI, Niveloni SI, Verdú EF, Ciacci C, Bai JC. Upper gastrointestinal endoscopic findings in celiac disease at diagnosis: A multicenter international retrospective study. World J Gastroenterol 2022; 28:6157-6167. [PMID: 36483156 PMCID: PMC9724482 DOI: 10.3748/wjg.v28.i43.6157] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/22/2022] [Accepted: 11/07/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease (CeD) in adults. Whether upper endoscopy helps detect comorbid conditions is unknown.
AIM To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis.
METHODS This is an observational, descriptive, multicenter, retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers. We collected data reported on first endoscopy, indicated for investigation of CeD. Diagnosis of CeD was performed by histology (≥ Marsh 2 type mucosal damage) and specific serology. Two European and one North American center included biopsy-confirmed CeD following positive serology. A fourth center (South America) included symptomatic patients undergoing endoscopy, irrespective of CeD serology. The latter cohort included a non-CeD control group.
RESULTS A total of 1328 patients (80% female; 35 years median age) were enrolled, of whom 95.6% had positive specific serology. In 135 patients, endoscopy revealed 163 abnormalities unrelated to CeD (prevalence: 10.1%). Erosive reflux esophagitis (6.4%), gastric erosions (2.0%), and suspicion of esophageal metaplasia (1.2%) were the most common findings. Biopsy-confirmed Barrett’s esophagus was infrequent (0.2%). No endoscopic cancer was detected. Older patients (≥ 51 years of age) had a higher prevalence of endoscopic findings than those ≤ 50 (P < 0.01). Within the South American cohort, CeD was associated with a lower rate (8.2%) of comorbid endoscopic findings compared with controls (29.1%; P < 0.001). In the adjusted multivariate analysis of this cohort, having CeD was associated with a 72% reduction in the risk of any endoscopic abnormality (P < 0.0001), and having alarm symptoms was associated with a 37% reduction in the risk of finding at least one endoscopic lesion (P < 0.02).
CONCLUSION In this large multicenter study, young adults with positive CeD serology had few comorbid endoscopic findings. Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage, no malignancy or premalignant lesions were found.
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Affiliation(s)
- Juan Pablo Stefanolo
- Small Bowel Section, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova 35124, Italy
- Gastroenterology Unit, Azienda Ospedale Università, Padova 35128, Italy
| | - Carolina Gizzi
- Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno 84081, Italy
| | - Ilaria Marsilio
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova 35124, Italy
| | - María Luján Espinet
- Small Bowel Section, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
| | - Edgardo Gustavo Smecuol
- Small Bowel Section, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
| | - Mark Khaouli
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton L8S 4K1, Canada
| | - María Laura Moreno
- Small Bowel Section, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
| | - María I Pinto-Sánchez
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton L8S 4K1, Canada
| | - Sonia Isabel Niveloni
- Small Bowel Section, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
| | - Elena F Verdú
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton L8S 4K1, Canada
| | - Carolina Ciacci
- Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno 84081, Italy
| | - Julio César Bai
- Small Bowel Section, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
- Research Institutes, Universidad del Salvador, Buenos Aires 1020, Argentina
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9
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Baykan AR, Cerrah S, Ciftel S, Vural MK, Kasap E. A No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: Can It Be Real? Cureus 2022; 14:e26521. [PMID: 35795577 PMCID: PMC9250690 DOI: 10.7759/cureus.26521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2022] [Indexed: 11/23/2022] Open
Abstract
Background and objective Pediatric guidelines on the diagnosis of celiac disease (CD) have reported that the positivity of anti-endomysium antibodies in the presence of anti-transglutaminase antibodies (TGA) 10 times higher than normal is sufficient for the diagnosis. In this study, we aimed to evaluate whether this diagnostic process for children can also be applied to adult patients. Materials and methods We retrospectively examined patients aged >18 years who were diagnosed with CD. The results of serological tests and endoscopic biopsy were evaluated. Patients with more than one month of duration between celiac serology and endoscopy, those diagnosed with CD before admission, those on a gluten-free diet, and those with selective IgA deficiency were excluded from the study. Results A total of 269 patients were included in the study. TGA value was significantly higher in patients with villous atrophy (p<0.001) and positively correlated with mucosal damage (r=0.60, p<0.01). Considering the cut-off value of 100 U/mL (>10 ULN) for the TGA antibodies, in line with the criteria regulated by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) for the diagnosis of CD, the sensitivity was 71.64%, the specificity was 100%, and the positive predictive value (PPV) was 100%. When the cut-off value was taken as 29.42 U/mL, the sensitivity was 100% and the specificity was 99.5%. For a TGA cut-off value of 52.7 U/mL (5.27 ULN), which determines the presence of partial or complete villous atrophy in the evaluation made considering mucosal damage, the sensitivity was 90%, the specificity was 100%, and the PPV was 100%. Conclusion Based on our findings, TGA titers were highly effective in demonstrating CD-related mucosal damage. This study endorses a biopsy-free strategy in adult patients in line with the ESPGHAN criteria. Local validation of test-specific thresholds will ensure that this approach has a significant impact on adult patients.
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10
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Enache I, Balaban DV, Vasilescu F, Jurcut C, Ionita-Radu F, Popp A, Matei D, Jinga M. Upper Gastrointestinal Tract Associated Lesions in Patients with Newly Diagnosed Celiac Disease. GASTROENTEROLOGY INSIGHTS 2022; 13:77-86. [DOI: 10.3390/gastroent13010009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
(1) Background: Currently available guidelines require upper gastrointestinal (GI) endoscopy with biopsy sampling for adult celiac disease (CD) diagnosis. Based on the pediatric experience, there has been a growing interest if serology-based diagnosis would be possible for adult CD also. Our aim was to analyze the associated upper GI tract lesions in newly diagnosed CD patients, to see if significant associated pathology is detected during index endoscopy, which might impact patient management not related to CD. (2) Methods: We performed a retrospective analysis of newly diagnosed CD cases diagnosed over a period of 7 years (2014–2020). Demographic, clinical, laboratory, endoscopy and histopathology data were collected from the patients’ charts. Diagnosis was set according to ACG Guideline 2013. (3) Results: Altogether 79 patients were recruited for this study purpose, 75.9% female, median age 39 years. All patients had positive CD-specific serology and atrophic mucosal injury in duodenal biopsy samples. Besides villous atrophy, associated endoscopic findings were detected in 42/79 (53.16%) of patients. Most of the gastric lesions were minor endoscopic findings—small sliding hiatal hernias, non-specific chronic gastritis, but we also found two cases of peptic ulcers, one case of metaplastic gastritis, six cases of atrophic gastritis and one subepithelial lesion. Only one patient had changes in the duodenum except CD-related findings—an inflammatory polyp in the duodenal bulb. No malignancies were found. (4) Conclusions: In our cohort, there was a significant number of newly diagnosed CD patients who had associated lesions during the index upper GI endoscopy, but most of them were minor endoscopic findings.
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Affiliation(s)
- Iulia Enache
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Dr. Carol Davila” Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Daniel Vasile Balaban
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Dr. Carol Davila” Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Florina Vasilescu
- “Dr. Carol Davila” Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Ciprian Jurcut
- “Dr. Carol Davila” Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Florentina Ionita-Radu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Dr. Carol Davila” Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Alina Popp
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Alessandrescu-Rusescu National Institute for Mother and Child Health, 020382 Bucharest, Romania
| | - Dumitru Matei
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Alessandrescu-Rusescu National Institute for Mother and Child Health, 020382 Bucharest, Romania
| | - Mariana Jinga
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Dr. Carol Davila” Central Military Emergency University Hospital, 010242 Bucharest, Romania
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11
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Losurdo G, Di Leo M, Santamato E, Arena M, Rendina M, Luigiano C, Ierardi E, Di Leo A. Serologic diagnosis of celiac disease: May it be suitable for adults? World J Gastroenterol 2021; 27:7233-7239. [PMID: 34876785 PMCID: PMC8611199 DOI: 10.3748/wjg.v27.i42.7233] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/02/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This "no biopsy" approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh's classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the "no biopsy" approach to CD diagnosis in patients outside the pediatric age.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Milena Di Leo
- Unit of Digestive Endoscopy, San Paolo Hospital, Milan 20090, Italy
| | - Edoardo Santamato
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Monica Arena
- Unit of Digestive Endoscopy, San Paolo Hospital, Milan 20090, Italy
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Carmelo Luigiano
- Unit of Digestive Endoscopy, San Paolo Hospital, Milan 20090, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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12
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Losurdo G, Di Leo M, Santamato E, Giangaspero A, Rendina M, Luigiano C, Ierardi E, Di Leo A. May Antitransglutaminase Levels Predict Severity of Duodenal Lesions in Adults with Celiac Disease? MEDICINA (KAUNAS, LITHUANIA) 2021; 57:1212. [PMID: 34833430 PMCID: PMC8622174 DOI: 10.3390/medicina57111212] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/03/2021] [Accepted: 11/04/2021] [Indexed: 01/11/2023]
Abstract
Background and Objective: Pediatric guidelines on celiac disease (CD) state that children with anti-transglutaminase antibodies (TGAs) >×10 upper limit of normal (ULN) may avoid endoscopy and biopsy. We aimed to evaluate whether these criteria may be suitable for villous atrophy diagnosis in CD adults. Materials and Methods: We retrospectively enrolled patients with CD aged >18 years. TGAs were expressed as xULN. Duodenal lesions were classified as atrophic or non-atrophic according to Marsh-Oberhuber. Fisher's exact and t-test were used for variables comparison. Receiver operating characteristics (ROC) curve analysis was performed with estimation of area under the curve (AUC), sensitivity, specificity, and positive and negative predictive value (PPV/NPV). Results: One hundred and twenty-one patients were recruited. Sixty patients (49.6%) had TGA >×10 ULN, and 93 (76.8%) had villous atrophy. The cut-off of >×10 ULN had sensitivity = 53.7%, specificity = 64.3%, PPV = 83.3%, and NPV = 29.5% to predict atrophy. Therefore, considering pediatric criteria, in 50 (41.3%) patients, biopsy could have been avoided. Patient subgroup with atrophy had higher TGA levels despite being not significant (37.2 ± 15.3 vs. 8.0 ± 1.3 ULN, p = 0.06). In adults, a slightly better diagnostic performance was obtained using a cut-off of TGA >×6.2 ULN (sensitivity = 57.1%, specificity = 65.6%, and AUC = 0.62). Conclusions: Despite our confirmation that villous atrophy is linked to high TGA levels, CD and atrophy diagnosis based only on serology is not reliable in adults.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (E.S.); (A.G.); (M.R.); (E.I.); (A.D.L.)
- Ph.D. Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Milena Di Leo
- Unit of Digestive Endoscopy, San Paolo Hospital, 20142 Milano, Italy; (M.D.L.); (C.L.)
| | - Edoardo Santamato
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (E.S.); (A.G.); (M.R.); (E.I.); (A.D.L.)
| | - Antonio Giangaspero
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (E.S.); (A.G.); (M.R.); (E.I.); (A.D.L.)
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (E.S.); (A.G.); (M.R.); (E.I.); (A.D.L.)
| | - Carmelo Luigiano
- Unit of Digestive Endoscopy, San Paolo Hospital, 20142 Milano, Italy; (M.D.L.); (C.L.)
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (E.S.); (A.G.); (M.R.); (E.I.); (A.D.L.)
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (E.S.); (A.G.); (M.R.); (E.I.); (A.D.L.)
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13
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Beig J, Rostami K, Hayman DTS, Hassan S, Gerred S, Ogra R. Is duodenal biopsy always necessary for the diagnosis of coeliac disease in adult patients with high anti-tissue transglutaminase (TTG) antibody titres? Frontline Gastroenterol 2021; 13:287-294. [PMID: 35722610 PMCID: PMC9186042 DOI: 10.1136/flgastro-2020-101728] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 06/08/2021] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE Avoiding duodenal biopsy in adults for coeliac disease (CD) diagnosis is controversial. Some retrospective and prospective studies have shown that CD can be reliably diagnosed in adults with serology rather than duodenal biopsies. This study aimed to check the accuracy of a cut-off value of ≥10 upper limit of normal of anti-tissue transglutaminase antibody (anti-TTG IgA) titres for CD diagnosis in adult patients. METHOD We retrospectively analysed adult patients (≥16 years) who underwent gastroscopy from 2013 to 2018 for positive coeliac serology. The relationship between titres and disease was determined by using linear models, whereas sensitivity and specificity were assessed by receiver operator curve. RESULTS We analysed 144 newly anti-TTG antibody-positive adult patients with a median age of 48.5 years (IQR 32-62); among them, 86 (60%) patients had CD (Marsh III: n=68 and Marsh II and I: n=18) with a higher prevalence in females (n=59 (69%)) and Europeans (n=60 (70%)). Fifty (58%) patients with CD had colonoscopy and five (6%) had imaging; only six patients were diagnosed with additional conditions. An anti-TTG IgA titre cut-off value of 150 U/L was 100% specific for CD in our dataset, with 70% (95% CI: 60% to 88%) sensitivity for this patient group. CONCLUSION Coeliac serology using anti-TTG IgA with titres ≥10× normal value is an excellent predictor of CD, irrespective of age, gender and ethnicity. Duodenal biopsy may not be necessary in selected adult patients with CD, especially younger than 50 years of age without additional gastrointestinal red-flag signs and symptoms.
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Affiliation(s)
- Junaid Beig
- Gastroenterology and Hepatology, Middlemore Hospital - Counties Manukau DIstrict Health Board (CMDH), Auckland, New Zealand
| | - Kamran Rostami
- Gastroenterology and Hepatology, MidCentral District Health Board, Palmerston North, New Zealand
| | - David T S Hayman
- Molecular Epidemiology and Public Health Laboratory, School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Summer Hassan
- Gastroenterology and Hepatology, Middlemore Hospital - Counties Manukau DIstrict Health Board (CMDH), Auckland, New Zealand
| | - Stephen Gerred
- Gastroenterology and Hepatology, Middlemore Hospital - Counties Manukau DIstrict Health Board (CMDH), Auckland, New Zealand
| | - Ravinder Ogra
- Gastroenterology and Hepatology, Middlemore Hospital - Counties Manukau DIstrict Health Board (CMDH), Auckland, New Zealand
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14
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Penny HA, Raju SA, Lau MS, Marks LJ, Baggus EM, Bai JC, Bassotti G, Bontkes HJ, Carroccio A, Danciu M, Derakhshan MH, Ensari A, Ganji A, Green PHR, Johnson MW, Ishaq S, Lebwohl B, Levene A, Maxim R, Mohaghegh Shalmani H, Rostami-Nejad M, Rowlands D, Spiridon IA, Srivastava A, Volta U, Villanacci V, Wild G, Cross SS, Rostami K, Sanders DS. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut 2021; 70:876-883. [PMID: 33139268 PMCID: PMC8040155 DOI: 10.1136/gutjnl-2020-320913] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 06/29/2020] [Accepted: 07/18/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.
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Affiliation(s)
- Hugo A Penny
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Suneil A Raju
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Michelle S Lau
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Lauren Js Marks
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Elisabeth Mr Baggus
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Julio C Bai
- Medicine, Gastroenterology Hospital 'Dr C Bonorino Udaondo', Buenos Aires, Argentina
| | - Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of Medicine, University of Perugia Medical School, Perugia, Italy
| | - Hetty J Bontkes
- Department Clinical Chemistry, Amsterdam Gastroenterology and Metabolism and Infection and Immunity Institutes, Amsterdam UMC, Amsterdam, The Netherlands
| | - Antonio Carroccio
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Mihai Danciu
- Pathology Department, Grigore T. Popa University of Medicine and Pharmacy Iasi, Iasi, Romania
| | | | - Arzu Ensari
- Department of Pathology, Ankara University Medical School, Ankara, Turkey
| | - Azita Ganji
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Peter H R Green
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Matt W Johnson
- Gastroenterology, Luton and Dunstable Hospital NHS Foundation Trust, Luton, UK
| | - Sauid Ishaq
- Department of Gastroenterology, Dudley Group NHS Foundation Trust, Birmingham City University, Birmingham, UK
| | - Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Adam Levene
- Gastroenterology, Luton and Dunstable Hospital NHS Foundation Trust, Luton, UK
| | - Roxana Maxim
- Gastroenterology Department, Grigore T. Popa University of Medicine and Pharmacy Iasi, Iasi, Romania
| | - Hamid Mohaghegh Shalmani
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - David Rowlands
- Department of Gastroenterology, Queen Elizabeth II Hospital, Hertfordshire, UK
| | - Irene A Spiridon
- Pathology Department, Grigore T. Popa University of Medicine and Pharmacy Iasi, Iasi, Romania
| | | | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Graeme Wild
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Simon S Cross
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Kamran Rostami
- Department of Gastroenterology, MidCentral District Health Board, Palmerston North, New Zealand
| | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
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15
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Loughrey MB, Shepherd NA. The indications for biopsy in routine upper gastrointestinal endoscopy. Histopathology 2020; 78:215-227. [PMID: 33382487 DOI: 10.1111/his.14213] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022]
Abstract
This review describes the indications and contraindications for endoscopic biopsy, in routine practice, of the upper gastrointestinal (GI) tract. We accept that this review provides grounds for controversy, as our stance in certain situations is counter to some national guidelines. Nevertheless, we provide evidence to support our viewpoints, especially on efficiency and economic grounds. We describe the particular controversies concerning the biopsy assessment of Barrett's oesophagus, chronic gastritis and the duodenum in the investigation of coeliac disease. We accept that there are indications for more extensive upper GI biopsy protocols in children than in adults; the latter constitute our main focus in this article. We would encourage detailed discussion between pathologists and their endoscopy colleagues about the indications, or lack of them, for routine upper GI endoscopic biopsy, as studies have shown that adherence to agreed guidelines has resulted in a very considerable diminution in the biopsy workload without compromising patient management. Furthermore, where biopsy is indicated, we emphasise the importance of accompanying clinical information provided to the pathologist, in particular regarding biopsy site(s), and regular feedback to endoscopists to improve and maintain the quality of such information. Finally, local dialogue is also advised, when necessary, to indicate to endoscopists the need to appropriately segregate biopsies into separate, individually labelled specimens, to maximise the information that can be derived by pathological evaluation and thereby improve the quality of the final pathology report.
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Affiliation(s)
- Maurice B Loughrey
- Department of Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK
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16
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Low prevalence of upper endoscopic gastrointestinal findings despite high frequency of alarm symptoms at the time of diagnosis in adult coeliac disease. Eur J Gastroenterol Hepatol 2020; 32:1447-1451. [PMID: 32675775 DOI: 10.1097/meg.0000000000001829] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Exclusion of organic disorders involving the upper gastrointestinal (UGI) is a mandatory step before considering a biopsy-avoidance diagnostic strategy for adult coeliac disease. We aim to evaluate the prevalence of alarm symptoms and coincidental UGI endoscopic findings at the time of diagnosis of coeliac disease. To develop consensus criteria to identify patients with coeliac disease requiring a gastroscopy and to evaluate whether alarm symptoms prompting gastroscopy were predictive of endoscopic findings. METHODS Presenting symptoms and UGI endoscopic findings at diagnosis of coeliac disease were collected retrospectively in 278 adult patients with coeliac disease diagnosed in Pavia between January 1999 and December 2017. A panel of experts developed criteria to evaluate which clinical scenarios warrant gastroscopy, which was then applied retrospectively to patients diagnosed in Pavia. RESULTS At least one alarm symptom was present in 177/278 patients, 121/278 met our criteria for gastroscopy. Major UGI endoscopic findings included 3 cases of autoimmune atrophic gastritis, 19 oesophagitis and 20 Helicobacter pylori infections. No organic disorders were found. Prevalence of major endoscopic findings did not differ between patients who met our criteria and those who did not. CONCLUSIONS Despite the high prevalence of alarm symptoms at diagnosis, coincident major UGI endoscopic findings are rare in adult coeliac disease. These results may be relevant for future developments in coeliac disease diagnosis in adults.
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Lund F, Pedersen MF, Kristiansen S. Estimation of the celiac disease prevalence in Denmark and the diagnostic value of HLA-DQ2/DQ8. Scandinavian Journal of Clinical and Laboratory Investigation 2020; 80:667-671. [DOI: 10.1080/00365513.2020.1829698] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Flemming Lund
- Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark
| | - Merete Frejstrup Pedersen
- Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark
| | - Søren Kristiansen
- Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark
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18
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Johnston RD, Chan YJ, Mubashar T, Bailey JR, Paul SP. No-biopsy pathway following the interim BSG guidance reliably diagnoses adult coeliac disease. Frontline Gastroenterol 2020; 13:73-76. [PMID: 34966534 PMCID: PMC8666863 DOI: 10.1136/flgastro-2020-101624] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/22/2020] [Accepted: 09/23/2020] [Indexed: 02/04/2023] Open
Abstract
Recent interim guidance from the British Society of Gastroenterology, aligned to historical paediatric practice, advises a no-biopsy protocol (NBP) for adults with high anti-tissue transglutaminase (tTG-IgA) titres and other clinical factors. A 7-year retrospective review identified 433 patients with positive tTG-IgA. Of these 433, 98 (23%) fulfilled the high titre criteria for an NBP which may have reduced endoscopic burden on the service. A high titre versus low titre translated in a 95% versus 75% histological confirmation of coeliac disease (p<0.01). The addition of anti-endomysial antibody analyses impacted minimally on these predictive rates. Our data support an NBP approach for selected patients. Of concern, however, was the finding that a third of patients with positive titres were not referred for a biopsy despite national guidance at the time advocating it. A clear message needs to be transmitted that the NBP is only for those with high titre, as opposed to any tTG-IgA positivity.
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Affiliation(s)
| | - Ying Jenny Chan
- Paediatrics, Torbay Hospital, Torquay, UK,Peninsula Medical School, University of Plymouth, Plymouth, UK
| | | | | | - Siba Prosad Paul
- Paediatrics, Torbay Hospital, Torquay, UK,Paediatrics, Yeovil District Hospital, Yeovil, UK
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19
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Ylönen V, Lindfors K, Repo M, Huhtala H, Fuchs V, Saavalainen P, Musikka A, Laurila K, Kaukinen K, Kurppa K. Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities. Nutrients 2020; 12:nu12092736. [PMID: 32911716 PMCID: PMC7551634 DOI: 10.3390/nu12092736] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 09/01/2020] [Accepted: 09/04/2020] [Indexed: 02/07/2023] Open
Abstract
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.
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Affiliation(s)
- Venla Ylönen
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (V.Y.); (K.L.); (M.R.); (V.F.); (A.M.); (K.K.)
| | - Katri Lindfors
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (V.Y.); (K.L.); (M.R.); (V.F.); (A.M.); (K.K.)
| | - Marleena Repo
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (V.Y.); (K.L.); (M.R.); (V.F.); (A.M.); (K.K.)
- Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland;
- Department of Pediatrics, Tampere University Hospital, 33520 Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, 33520 Tampere, Finland;
| | - Valma Fuchs
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (V.Y.); (K.L.); (M.R.); (V.F.); (A.M.); (K.K.)
| | - Päivi Saavalainen
- Research Programs Unit, Immunobiology, and Haartman Institute, Department of Medical Genetics, University of Helsinki, 00014 Helsinki, Finland;
| | - Alex Musikka
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (V.Y.); (K.L.); (M.R.); (V.F.); (A.M.); (K.K.)
| | - Kaija Laurila
- Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland;
| | - Katri Kaukinen
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (V.Y.); (K.L.); (M.R.); (V.F.); (A.M.); (K.K.)
- Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland;
- Department of Pediatrics, Tampere University Hospital, 33520 Tampere, Finland
- The University Consortium of Seinäjoki, 66320 Seinäjoki, Finland
- Department of Pediatrics, Seinäjoki Central Hospital, 66320 Seinäjoki, Finland
- Correspondence: ; Tel.: +358-50-318-6255
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20
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Abstract
OBJECTIVES The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guidelines, enabled for the first time, a nonbiopsy approach in the diagnosis of celiac disease (CD). We aimed to prospectively assess 4 tissue-transglutaminase (tTg) IgA assays of 4 random-access analyzers and examine their accuracy in diagnosing CD without a biopsy. METHODS We enrolled 186 consecutive children referred to upper endoscopy and intestinal biopsy. One group included 109 patients with positive tTg that was referred for suspected CD. Another group included 77 patients with negative tTg referred because of other indications. All participants had a blood sample taken at the time of endoscopy. Samples were tested with 4 tTg IgA assays on automated analyzers and 1 Elisa kit. All intestinal biopsies were evaluated by a local pathologist, a central pathologist, and a CD expert blinded to each other. CD was diagnosed when full agreement was reached. Analytical performance of the assays included precision with controls and samples, lot to lot variation, and carryover. RESULTS In our cohort, all tested tTg IgA-automated assays showed sensitivities above 98% and specificities above 99%. ROC analysis demonstrated AUC (area under the curve) >0.99 for all 4 analyzers. The positive-predictive values (PPV) were all >0.99 and negative-predictive values (NPV) were >0.97. The Elisa kit had sensitivity of 95%, specificity of 96%, AUC of 0.96, PPV of 0.98 and NPV of 0.93. CONCLUSION CD can be accurately diagnosed without biopsy based on tTg IgA levels at least 10 times the ULN using the 4 high-volume random-access analyzers used in our study.
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21
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Penny HA, Raju SA, Sanders DS. Progress in the serology-based diagnosis and management of adult celiac disease. Expert Rev Gastroenterol Hepatol 2020; 14:147-154. [PMID: 32011187 DOI: 10.1080/17474124.2020.1725472] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Introduction: This article provides a comprehensive overview of the development and application of serological tests used routinely in clinical practice for the diagnosis and management of adult celiac disease.Areas covered: We summarize existing scientific literature related to anti-endomyseal, anti-tissue transglutaminase, and anti-deamidated gliadin peptide antibodies and detail the current and potential future applications of these tests in celiac disease.Expert commentary: Current serological tests in celiac disease have some of the best performance characteristics among disease-specific tests. However, in adult celiac disease, current diagnostic algorithms still rely on duodenal biopsies to confirm the diagnosis. A 'biopsy avoidance strategy' has been implemented in pediatric celiac disease. Future high-quality studies will help inform on whether this approach can be implemented into adult gastroenterology services. It is envisaged that the next 5 years will see an increasing reliance on serology in the diagnosis of adult celiac disease.
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Affiliation(s)
- Hugo A Penny
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.,Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK
| | - Suneil A Raju
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - David S Sanders
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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22
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Ho SSC, Keenan JI, Day AS. The Role of Gastrointestinal-Related Fatty Acid-Binding Proteins as Biomarkers in Gastrointestinal Diseases. Dig Dis Sci 2020; 65:376-390. [PMID: 31529416 DOI: 10.1007/s10620-019-05841-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 09/10/2019] [Indexed: 12/14/2022]
Abstract
The fatty acid-binding proteins play a major role in intracellular transportation of long-chain fatty acids. Nine fatty acid-binding proteins have been identified, with each having individual tissue-specific functions in addition to regulation of fatty acids. This review focuses on the three fatty acid-binding proteins found in the gastrointestinal tract and discusses their role as diagnostic or disease monitoring markers in neonatal necrotizing enterocolitis, acute mesenteric ischemia, celiac disease, and inflammatory bowel disease. Of these three fatty acid-binding proteins, intestinal fatty acid-binding protein is of the most interest due to its exclusive expression in the gastrointestinal tract. The elevation of intestinal fatty acid-binding protein in blood and urine reflects enterocyte damage, regardless of the underlying cause. The short half-life of intestinal fatty acid-binding protein also means it is a relatively sensitive marker. In contrast, there is currently less evidence to support liver fatty acid-binding protein and ileal bile acid-binding protein as sensitive biomarkers in these conditions. More extensive studies with specific endpoints are required to validate the roles of these fatty acid-binding proteins in gastrointestinal diseases.
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Affiliation(s)
- Shaun S C Ho
- Department of Paediatrics, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand
| | - Jacqueline I Keenan
- Department of Surgery, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand.
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23
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Abstract
Celiac disease is a gluten-triggered immune-mediated disorder, characterized by inflammation of the enteric mucosa following lymphocytic infiltration and eventually resulting in villous blunting. There have been many developments in refining diagnostic laboratory tests for celiac disease in the last decade. Biopsy-sparing diagnostic guidelines have been proposed and validated in a few recent prospective studies. However, despite these developments, histologic evaluation of duodenal mucosa remains one of the most essential diagnostic tools as it helps in the diagnosis of celiac disease in individuals who do not fulfill the biopsy-sparing diagnostic criteria and in those not responding to a gluten-free diet. Histologic evaluation also allows for the assessment of mucosal recovery after treatment and in the identification of concurrent intestinal diseases. Therefore, pathologists should be familiar with the histologic spectrum of celiac disease and need to be aware of other disorders with similar symptoms and histopathology that may mimic celiac disease. This review aims to provide pathologists with updates on celiac laboratory testing, biopsy-sparing diagnostic criteria, histopathology, complications, and differential diagnoses of celiac disease.
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24
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Diagnosing Celiac Disease: Towards Wide-Scale Screening and Serology-Based Criteria? Gastroenterol Res Pract 2019; 2019:2916024. [PMID: 31467522 PMCID: PMC6701393 DOI: 10.1155/2019/2916024] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 07/16/2019] [Indexed: 12/12/2022] Open
Abstract
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.
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25
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Fuchs V, Kurppa K, Huhtala H, Laurila K, Mäki M, Collin P, Salmi T, Luostarinen L, Saavalainen P, Kaukinen K. Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities. Aliment Pharmacol Ther 2019; 49:277-284. [PMID: 30592070 DOI: 10.1111/apt.15109] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 10/25/2018] [Accepted: 12/02/2018] [Indexed: 12/19/2022]
Abstract
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.
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Affiliation(s)
- Valma Fuchs
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Tampere Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - Kaija Laurila
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Markku Mäki
- Tampere Center for Child Health Research, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | - Pekka Collin
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Teea Salmi
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Liisa Luostarinen
- Department of Neurology, Päijät-Häme Central Hospital, Lahti, Finland
| | - Päivi Saavalainen
- Research Programs Unit, Immunobiology, and Haartman Institute, Department of Medical Genetics, University of Helsinki, Helsinki, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
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26
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Boutrid N, Rahmoune H, Amrane M. Genetics and serology of celiac disease during giardiasis. Scand J Gastroenterol 2018; 53:1427. [PMID: 30353768 DOI: 10.1080/00365521.2018.1508612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 07/28/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Nada Boutrid
- a Department of Pediatrics, Setif University Hospital , Setif-1 University , Setif , Algeria
| | - Hakim Rahmoune
- a Department of Pediatrics, Setif University Hospital , Setif-1 University , Setif , Algeria
| | - Mounira Amrane
- b Genetic, Cardiovascular and Nutritional Diseases Laboratory , Setif-1 University , Setif , Algeria
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27
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Does biopsy still have a role for adult coeliac disease? Lancet Gastroenterol Hepatol 2018; 2:773-774. [PMID: 29017708 DOI: 10.1016/s2468-1253(17)30251-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 07/21/2017] [Indexed: 12/26/2022]
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28
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Abstract
Celiac disease is a common autoimmune disorder of the small intestine, triggered by an immunological response to the gluten present in wheat, barley, and rye in individuals who are genetically at risk. A key to reducing the complications of this disease is early diagnosis, preferably in childhood, and consuming a lifelong gluten-free diet once diagnosis is confirmed. Yet, the diagnosis of celiac disease is often considerably delayed, exposing patients to needless suffering and morbidity. It is also difficult to confirm histologically if dietary gluten has been restricted prior to obtaining a diagnostic biopsy, a significant problem given the current growing popularity of gluten-free diets. Furthermore, failure to understand or follow current guidelines means physicians may recommend patients commence the gluten-free diet before initiating referral to a gastroenterologist. Finally, adding further confusion, pediatric guidelines in Europe support a diagnosis based on serology rather than on histology, whereas those based in North America do not. The purpose of this review is to discuss these issues and other controversies in the diagnosis of celiac disease and to consider ways to optimize diagnosis across the lifespan.
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Affiliation(s)
- Justine M Turner
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada.
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29
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Di Tola M, Casale R, Marino M, Borghini R, Occhiuzzi U, Picarelli A. Anti-transglutaminase detection followed by endomysium antibody confirmation test on monkey esophagus is the best strategy to screen for celiac disease. Scand J Clin Lab Invest 2018; 78:243-244. [PMID: 29313382 DOI: 10.1080/00365513.2018.1424350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 01/02/2018] [Indexed: 06/07/2023]
Affiliation(s)
- Marco Di Tola
- a Department of Internal Medicine and Medical Specialties , Sapienza University , Rome , Italy
- b Department of Biomedical Services - UOC Laboratory Analysis Marsica/Peligno/Sangrina Area , Avezzano , Italy
| | - Rossella Casale
- a Department of Internal Medicine and Medical Specialties , Sapienza University , Rome , Italy
| | - Mariacatia Marino
- a Department of Internal Medicine and Medical Specialties , Sapienza University , Rome , Italy
| | - Raffaele Borghini
- a Department of Internal Medicine and Medical Specialties , Sapienza University , Rome , Italy
| | - Umberto Occhiuzzi
- b Department of Biomedical Services - UOC Laboratory Analysis Marsica/Peligno/Sangrina Area , Avezzano , Italy
| | - Antonio Picarelli
- a Department of Internal Medicine and Medical Specialties , Sapienza University , Rome , Italy
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