Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus

Abstract

ObjectiveDifferential diagnosis of villous atrophy (VA) without coeliac antibodies in adults includes seronegative coeliac disease (CD) and chronic enteropathies unrelated to gluten, ie. non-coeliac enteropathies (NCEs). There is currently no international consensus on the nomenclature and diagnostic criteria for these enteropathies. In this work, a Delphi process was conducted to address this diagnostic and clinical uncertainty.DesignAn international task force of 13 gastroenterologists from six countries was recruited at the 16th International Coeliac Disease Symposium, Paris, 2019. Between September 2019 and July 2021, a Delphi process was conducted through mail surveys to reach a consensus on which conditions to consider in the differential diagnosis of VA with negative coeliac serology and the clinical diagnostic approaches required for these conditions. A 70% agreement threshold was adopted.ResultsChronic enteropathies characterised by VA and negative coeliac serology can be attributed to two main clinical scenarios: forms of CD presenting with negative serology, which also include seronegative CD and CD associated with IgA deficiency, and NCEs, with the latter recognising different underlying aetiologies. A consensus was reached on the diagnostic criteria for NCEs assisting clinicians in differentiating NCEs from seronegative CD. Although in adults seronegative CD is the most common aetiology in patients with VA and negative serology, discriminating between seronegative CD and NCEs is key to avoid unnecessary lifelong gluten-free diet, treat disease-specific morbidity and contrast poor long-term outcomes.ConclusionThis paper describes the Paris consensus on the definitions and diagnostic criteria for seronegative CD and chronic NCEs in adults.

DQA1*0102 DQB1*0602 haplotype distinguishes coeliac disease and its complications from gluten unrelated enteropathies

“…Finally, the seronegative CD is a rare form of CD with negative coeliac-specific antibodies. Diagnosis of this condition relies on histological response to a GFD, and a finding of HLA-DQ2/DQ8 molecules, after the exclusion of all other causes of NCE [1,3,6,7].…”

“…These conditions are a cluster of heterogeneous conditions aetiologically unrelated to each other. Because they all share a similar clinical picture, a poor prognosis and a difficult differential diagnosis with CD and its complications, they have been grouped together and defined as noncoeliac enteropathies (NCE) [1]. They include autoimmune enteropathy, villous atrophy associated with common variable immune deficiency, iatrogenic enteropathies, particularly angiotensin II receptor blockers-associated enteropathy, primary small-bowel lymphomas, infectious forms, tropical sprue, Crohn's disease and idiopathic villous atrophy [1][2][3][4][5].…”

Seronegative coeliac disease and non-coeliac enteropathies: precision medicine, precision medicine, where are you?

“…It is well described that IgG antibodies to either TG2, IgG antibodies to deamidated gliadin peptides and IgG antibodies to endomysium (EMA test, where the endomysium antigen is in fact TG2) occur. This is now adequately discussed in the paper by Schiepatti et al ,1 and reflected in the current strategy of many coeliac serology panels to measure IgA-TG2 and IgG-DGP in the same serum sample. Alternatively, measure IgA-TG2 and total IgA in the first round and then IgG-based test in the second.…”

“…In a very recent and welcome article, Schiepatti et al address a challenging field of gastroenterology 1. Whereas the diagnosis of coeliac disease in most cases is simple, although overlooked, there are other circumstances where this is much more difficult.…”

Genetic Diagnosis Guides Treatment of Autoimmune Enteropathy

“…Autoimmune enteropathy (AIE) is a severe form of enteropathy characterized by chronic diarrhea refractory to any exclusion diet and associated with autoimmunity. 1 , 2 Despite this clear definition, diagnosis is challenging. The presence of antienterocyte antibodies against the AIE-75kDa antigen 3 is a strong but inconstant biomarker.…”