Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis

Kabbani, Toufic; Vanga, Rohini R.; Leffler, Daniel A.; Villafuerte-Gálvez, Javier; Pallav, Kumar; Hansen, Joshua; Mukherjee, Rupa; Dennis, Melinda; Kelly, Ciarán P.

doi:10.1038/ajg.2014.41

Cited by 83 publications

(62 citation statements)

References 24 publications

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“…Unfortunately, much of the clinical world has not yet grasped the idea that gluten can trigger autoimmune disorders other than CD, which leads to misleading notions that only CD patients have to be strict with the gluten-free diet (GFD), while NCGS patients can "cheat" once-ina-while. Statements such as, patients with "NCGS can be more liberal and titrate their exposure to gluten as needed to avoid symptoms, " [53] can be harmful to the patient. CD is a gastrointestinal disorder in which patients make elevated IgA to gliadin and tissue transglutaminse-2.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens

Lambert¹,

Vojdani²

2017

J Clin Cell Immunol

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Section: Discussionmentioning

confidence: 99%

Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens

Lambert¹,

Vojdani²

2017

J Clin Cell Immunol

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“…The recently published diagnostic model (Figure 1) for symptoms responsive to a GFD by Kabbani et al can be very helpful in differentiating CD from NCGS. [154]. This model can be employed to differentiate between CD and NCGS after ruling out WA with IgE assays when it is suspected based on signs of an allergic etiology such as hives, urticaria, angioedema or eczema.…”

Section: Functional Assays (Fa) or Food Challenge Testmentioning

confidence: 99%

Gluten and the Gut: A Brief Review of Gluten-Related Gastrointestinal Disorders

Shah¹

2017

SOJI

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We conducted online electronic searches (published manuscripts in English) of the Cochrane Library, pub med and manual searches of selected specialty journals to identify any pertinent literature. The search was conducted using the key words 'celiac disease', 'gluten related disorder', 'non celiac gluten sensitivity', 'wheat allergy', 'gluten', , 'gluten free diet'. Studies not published in English or published only in the abstract form were excluded. We also conducted a focused review of available references to identify subsequent pertinent papers. AbstractCeliac disease (CD) was the first gluten-related disorder to be described. Presently the realm of gluten-related disorders also includes non-celiac gluten sensitivity (NCGS) and wheat allergy (WA). CD is a multisystem immune mediated enteropathy observed in genetically susceptible individuals exposed to dietary gluten present in barley, rye and wheat. Although the prevalence of CD is on the rise, it still largely remains under diagnosed given that many cases can be silent, subtle or atypical. The Pathophysiology of CD includes both innate and adaptive immune response to dietary gluten. Patients present with a wide variety of intestinal and extra-intestinal symptoms and are at risk for non-Hodgkin's lymphoma and small intestinal adenocarcinoma. The corner stone for treatment of CD is a gluten-free diet (GFD). NCGS is an emerging condition associated with gluten ingestion and the diagnosis of which is based on exclusion of CD and WA. Further evidence and studies are required to fully appreciate the clinical entity of NCGS and WA to detail its epidemiology and pathogenesis. The symptoms of NCGS and WA may overlap with CD and hence it is imperative to differentiate these clinical entities and select patients for appropriate management.Keywords: Celiac disease, gluten related disorder, non-celiac gluten sensitivity, wheat allergy, gluten, epidemiology, clinical features, Pathophysiology, management, gluten free diet.Core tip: CD is largely under-diagnosed while the incidence and prevalence of gluten-related disorders are on the rise. A clear understanding of the various clinical presentations of gluten-related disorders can help differentiate CD from NCGS and WA. The management for these conditions differs and hence accurate diagnosis leads to improved patient outcomes with avoidance of longterm complications as well as unnecessary testing which can be both invasive and expensive. Celiac DiseaseThe term celiac is derived from the Greek word "koiliaks" meaning "abdominal". It was first described in the second century in modern day Turkey by a Greek physician Aretaeus of Cappadocia [1]. In 1888, Samuel Gee; a pediatrician from the United Kingdom gave the first modern-day description of the condition and associated diet to the treatment of celiac disease EpidemiologyCeliac disease occurs in about 1% of the general population worldwide [7]. Data from the USA suggests CD to be more common in Caucasians as compared to African-Americans and Hispanics [8,9]. The initial ...

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“…It has been suggested that where available negative human leucocyte antigen DQ2 and DQ8 genotype is useful, in that in can exclude CD with certainty given its 100 % negative predictive value; this will account for almost half of presenting cases (31) . However, if human leucocyte antigen-DQ typing is not readily available, or is positive, then a gluten challenge followed by coeliac investigations is required (46) . Traditionally, a gluten challenge has been suggested to be ≥10 g gluten (equivalent to about 4 slices of bread) daily for 6 weeks, prior to formalised testing.…”

Section: How To Diagnose Non-coeliac Gluten Sensitivitymentioning

confidence: 99%

“…To date, the reference standard for the diagnosis of 'true' NCGS is an elimination diet followed by double-blind placebocontrolled gluten challenge, a method which could hardly be introduced into clinical practice (11) . Recently, a diagnostic algorithm based on the absence or presence of clinical, serologic and histological criteria has been proposed to diagnose and differentiate NCGS from CD (46) . This novel study provides a clinically pragmatic approach as it takes into consideration the difficulties that arise when evaluating patients who present with gluten-based sensitivity and are already taking a GFD, which in cases of CD can lead to negative coeliac serology and normal duodenal biopsies (46) .…”

Section: How To Diagnose Non-coeliac Gluten Sensitivitymentioning

confidence: 99%

“…Recently, a diagnostic algorithm based on the absence or presence of clinical, serologic and histological criteria has been proposed to diagnose and differentiate NCGS from CD (46) . This novel study provides a clinically pragmatic approach as it takes into consideration the difficulties that arise when evaluating patients who present with gluten-based sensitivity and are already taking a GFD, which in cases of CD can lead to negative coeliac serology and normal duodenal biopsies (46) . It has been suggested that where available negative human leucocyte antigen DQ2 and DQ8 genotype is useful, in that in can exclude CD with certainty given its 100 % negative predictive value; this will account for almost half of presenting cases (31) .…”

Section: How To Diagnose Non-coeliac Gluten Sensitivitymentioning

confidence: 99%

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The rise and fall of gluten!

2015

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Mankind has existed for 2·5 million years but only in the last 10 000 years have we been exposed to wheat. Wheat was first cultivated in the Fertile Crescent (South Western Asia) with a farming expansion that lasted from about 9000BC to 4000BC. Thus it could be considered that wheat (and gluten) is a novel introduction to man's diet! Prior to 1939 the rationing system had already been devised. This led to an imperative to try to increase agricultural production. Thus it was agreed in 1941 that there was a need to establish a Nutrition Society. The very roots of the society were geared towards necessarily increasing the production of wheat. This goal was achieved and by the end of the 20th century, global wheat output had expanded 5-fold. Perhaps as a result the epidemiology of coeliac disease (CD) or gluten sensitive enteropathy has changed. CD is a state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals. CD now affects 1 % or more of all adults, for which the treatment is a strict lifelong gluten-free diet. However, there is a growing body of evidence to show that a far greater proportion of individuals without coeliac disease are taking a gluten-free diet of their own volition. This clinical entity has been termed non-coeliac gluten sensitivity (NCGS), although the condition is fraught with complexities due to overlap with other gluten-based constituents that can also trigger similar clinical symptoms. This review will explore the relationship between gluten, the rising prevalence of modern coeliac disease, and the new entity of NCGS along with its associated uncertainties.

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Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis

Cited by 83 publications

References 24 publications

Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens

Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens

Gluten and the Gut: A Brief Review of Gluten-Related Gastrointestinal Disorders

The rise and fall of gluten!

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