Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice

Werkstetter, Katharina; Korponay-Szabó, Ilma Rita; Popp, Alina; Villanacci, Vincenzo; Salemme, Marianna; Heilig, G.H.J.; Lillevang, Søren Thue; Mearin, M. Luisa; Ribes-Koninckx, Carmen; Thomas, Adrian G; Troncone, Riccardo; Filipiak, Birgit; Mäki, Markku; Gyimesi, Judit; Najafi, Mehri; Dolinšek, Jernej; Sander, Stine Dydensborg; Auricchio, Renata; Papadopoulou, Alexandra; Vécsei, Andreas; Szitányi, Peter; Donat, Ester; Nenna, Raffaella; Alliët, Philippe; Penagini, Francesca; Garnier-Lengliné, Hélène; Castillejo, Gemma; Kurppa, Kalle; Shamir, Raanan; Hauer, Almuthe; Smets, Françoise; Corujeira, Susana; Winckel, Myriam Van; Buderus, Stephan; Chong, Sonny K. F.; Husby, Steffen; Koletzko, Sibylle; Socha, Piotr; Cukrowská, Božena; Szajewska, Hania; Wyhowski, J; Brown, Nailah; Batra, Gauri; Mišak, Zrinjka; Seiwerth, Sven; Dmitrieva, Yulia; Abramov, D. S.; Vandenplas, Yvan; Goossens, Alain; Schaart, Maaike W.; Smit, Vincent T.H.B.M.; Kalach, Nicolas; Gosset, Pierre; Kovács, Judit B.; Nagy, A; Lellei, Ilona; Kőbányai, Rita; Khatami, Katayoun; Monajemzadeh, Maryam; Dimakou, K.; Patereli, Amalia; Hansen, Tine Plato; Kavalar, Rajko; Bolonio, Miguel; Ramos, David; Kogler, Hubert; Amann, Gabriele; Kosova, R.; Maglio, Mariantonia; Janssens, Elke; Achten, Ruth; Frühauf, Pavel; Skálová, Helena; Kirchner, Thomas; Petrarca, Laura; Magliocca, Fabio Massimo; Martinez, F. Rocuts; Morente, Vanesa; Thanner-Lechner, Sonja; Ratschek, Manfred; Gasparetto, Marco; Hook, Liz; Canioni, Danielle; Wanty, Catherine; Mourin, Anne; Laurila, Kaija; Vornane, Martine; Friedler, Vered Nachmias; Morgenstern, Sara; Dias, Jorge Amil; Carneiro, Fátima; Biervliet, S. Van; Velde, Saskia Vande; Banoub, Hany; Sampson, Steve; Müller, Annette; Ene, Adina; Rafeey, Mandana; Sadat, Amir Taher Eftekhar

doi:10.1053/j.gastro.2017.06.002

Cited by 229 publications

(215 citation statements)

References 40 publications

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“…This finding is similar to other validation studies proposing to omit biopsy for children with tTGIgA > 10-fold the upper normal limit, when associated with other criteria [5, 24, 27, 28]. …”

Section: Discussionsupporting

confidence: 90%

Identifying True Celiac Disease and Wheat Allergy in the Era of Fashion Driven Gluten-Free Diets

Spoerl

Bastid²,

Ramadan

et al. 2019

Int Arch Allergy Immunol

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Background: Diagnosing both celiac disease (CD) and wheat allergy (WA) might be challenging due to the increasingly popular gluten-free diets. Objectives: This study investigates the value of anti-tissue transglutaminase IgA (tTGIgA) and wheat-specific IgE (WIgE), and identifies clinical and serological features associated with CD and WA. Method: Serological markers of autoimmunity and allergy along with medical charts of patients assessed for tTGIgA and WIgE between 2010 and 2016 were evaluated. Results: During the last years, an increasing number of patients have been tested for tTGIgA, while the number of positive results decreased linearly. Among the 2,965 patients included, 128 patients showed at least once a positive tTGIgA. All patients with tTGIgA levels higher than the 12-fold upper normal limit had CD. The ratio of tTGIgA/total IgA did not perform better as a diagnostic test for CD compared to tTGIgA. tTGIgA and anti-nuclear antibodies were significantly associated. WA was only rarely investigated, particularly in adults. However, positive WIgE were found in nearly 50% of the cases. WIgE and tTGIgA values were negatively correlated. Conclusions: tTGIgA were increasingly tested, while the rate of positive results decreased in recent years, possibly reflecting the impact of current alimentary trends on clinical practice. Associated autoimmune disease was frequently found in CD. High levels of tTGIgA accurately predicted CD diagnosis. WA was rarely investigated and deserves more attention, in particular in children with atopic background. WA does not seem to be associated with CD.

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Section: Discussionsupporting

confidence: 90%

Identifying True Celiac Disease and Wheat Allergy in the Era of Fashion Driven Gluten-Free Diets

Spoerl

Bastid²,

Ramadan

et al. 2019

Int Arch Allergy Immunol

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“…Altogether 33% of new coeliac disease patients could have been diagnosed applying the “triple criteria”, which might be even a conservative estimation as some subjects with a high likelihood for coeliac disease withdrew before the endoscopy. In the population‐based low‐risk cohort, the figure (48%) was close to that seen in paediatric studies . Besides being easier for patients, reduced endoscopies could provide substantial healthcare savings, as it is estimated that up to 95% of diagnostic expenses could be spared by omitting the biopsy .…”

Section: Discussionsupporting

confidence: 63%

“…One might ask whether laborious EMA was required in all cases, but currently it could be considered as inexpensive quality control. In contrast, HLA testing seems to add minimal value in adults with high tTG‐ab values and positive EMA, similarly as recently shown in children . Therefore, genotyping could be restricted to exclude coeliac disease in unclear cases …”

Section: Discussionmentioning

confidence: 84%

“…Another explanation for suboptimal PPV for serology in some studies could lie in the use of error‐prone biopsy results as the gold standard . Accordingly, Werkstetter et al observed remarkable variability in histopathological analyses between local and centralised providers even in a pre‐planned research setting. Only a few studies evaluating the nonbiopsy criteria have given satisfactory data on this issue, including the number and location of biopsies, handling and orientation of the samples, and histological interpretation.…”

Section: Discussionmentioning

confidence: 99%

“…Due to this and the aforesaid problems with the histology‐based diagnosis, the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) established in 2012 new criteria stating that the biopsy could be avoided in symptomatic children with tTG‐ab value more than 10 times the upper limit of normal (ULN), positive EMA, and coeliac‐type genotype . There is increasing evidence to support the accuracy of these guidelines for paediatric coeliac disease if applied meticulously …”

Section: Introductionmentioning

confidence: 99%

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

Fuchs

Kurppa

Huhtala

et al. 2018

Aliment Pharmacol Ther

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Summary 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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