Seronegative celiac disease: Shedding light on an obscure clinical entity

Volta, Umberto; Caio, Giacomo; Boschetti, Elisa; Giancola, Fiorella; Rhoden, Kerry J.; Ruggeri, Eugenio; Paterini, Paola; Giorgio, Roberto De

doi:10.1016/j.dld.2016.05.024

Cited by 89 publications

(102 citation statements)

References 30 publications

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“…Villous atrophy is an unspecific histological finding that can be found in other enteropathies unrelated to gluten . However, coeliac disease remains one of the most common causes of SNVA . Recent publications seem to suggest that seronegative coeliac disease show a poor prognosis and a higher risk of developing complications than seropositive coeliac disease .…”

Section: Discussionmentioning

confidence: 99%

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Gamma delta⁺ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Fernández‐Bañares

Crespo

Núñez

et al. 2020

Aliment Pharmacol Ther

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Summary Background The causes of seronegative villous atrophy can be grouped as coeliac or noncoeliac related. There is no consensus on how to approach subjects with seronegative coeliac disease. Aim To evaluate the accuracy of both an increase in CD3+ T‐cell receptor gamma delta+ (TCRγδ+) intraepithelial lymphocytes and coeliac lymphogram for the diagnosis of coeliac disease in patients with seronegative villous atrophy. Methods Sixty‐seven consecutive patients with seronegative villous atrophy were included. Duodenal biopsies to assess TCRγδ+ and CD3− by flow cytometry were performed at the index endoscopy. Coeliac lymphogram was defined as an increase in TCRγδ+ plus a decrease in CD3− intraepithelial lymphocytes. Sensitivity, specificity and Fagan's nomogram were calculated. Results Coeliac disease was diagnosed in 37 patients and noncoeliac villous atrophy in 30. Coeliac patients were younger (39 ± 3 vs 55 ± 3 years; P = 0.001), more often showed HLA‐DQ2/8 (97.6% vs 61%; P = 0.002) and had a more severe histology (61% vs 32% Marsh 3b‐c; P = 0.055), as compared to noncoeliac ones. Coeliac lymphogram was associated with a sensitivity of 87% (CI, 73.7‐95) and specificity of 96.7% (82.7‐99.9), whereas evaluating only TCRγδ+ yielded a sensitivity of 91.3% (79.2‐97.6) and specificity of 83.3% (65.3‐94.3). Among patients with a pre‐test coeliac disease probability of 30%, post‐test probabilities were 92% and 5% for positive and negative coeliac lymphogram, and 70% and 4% for positive and negative TCRγδ+. Conclusions Coeliac lymphogram was associated with a high level of diagnostic evidence either against or in favour of coeliac disease in patients with seronegative villous atrophy.

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Section: Discussionmentioning

confidence: 99%

“…Causes of seronegative villous atrophy (SNVA) can be grouped as coeliac disease‐ or noncoeliac disease‐related. Coeliac disease is the most frequent cause of SNVA among patients of White ethnicity, accounting for up to 30% of these cases …”

Section: Introductionmentioning

confidence: 99%

Gamma delta⁺ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Fernández‐Bañares

Crespo

Núñez

et al. 2020

Aliment Pharmacol Ther

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“…The condition marked by mild enteropathy, celiac disease and negative serology has been described as seronegative celiac disease [24,25]. A conflicting debate has arisen in this context, since some researchers do not acknowledge the need for a gluten-free diet and suggest a watch-and-see strategy until serology becomes positive [26].…”

Section: Origin Of Mementioning

confidence: 99%

Lymphocytic duodenitis or microscopic enteritis and gluten-related conditions: what needs to be explored?

Ierardi¹,

Losurdo²,

Iannone³

et al. 2017

aog

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Microscopic enteritis (ME) is characterized by abnormal infiltration of intraepithelial lymphocytes in intestinal mucosa. It was described as duodenal lymphocytosis or lymphocytic duodenitis until the dedicated Consensus Conference of 2015. ME represents a common feature of several gluten-mediated and non-gluten related diseases; therefore, it is an umbrella term embracing several conditions. The most frequent causes of ME are gluten-related disorders (celiac disease, non-celiac gluten sensitivity, wheat allergy), Helicobacter pylori infection and drug-related damages. Less frequently, ME may be secondary to inflammatory bowel disease, some autoimmune conditions, immunoglobulin deficiencies, blood malignancies, infections and irritable bowel syndrome. Therefore, the differential diagnosis of ME may be challenging. The diagnosis of ME needs to be driven by predominant symptoms and patient history. However, it is often difficult to achieve an immediate identification of the underlying condition, and a broad variety of diagnostic tests may be required. Ultimately, long-term surveillance is needed for a final diagnosis in many cases, since a hidden or quiescent condition may be disclosed after a period of latency. In any case, strict collaboration between the clinician and the pathologist is pivotal. The treatment of ME should be personalized, depending on the underlying disease. For gluten-related conditions (celiac disease, gluten sensitivity, wheat allergy, dermatitis herpetiformis), a gluten-free diet may be proposed. For other conditions, a targeted etiologic treatment is necessary. In conclusion, ME represents a novel entity that is attracting increasing interest. The growing epidemiologic trend confirms that it will become a common condition in clinical practice.

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“…These patients had more than one seronegative antibody, positive genetic tests for CD, biopsies consistent with CD, responded to the gluten-free diets and tested negative for other causes of villous flattening [14]. As seronegative CD may be pathophysiologically distinct from seropositive CD, [15] the effects of PPIs on increasing intestinal permeability might be playing a role. [16, 17] However, our findings should be considered with caution given the small amount of patients (n=11) who presented with seronegative CD.…”

Section: Discussionmentioning

confidence: 99%

The impact of acid suppression medications and non-steroidal anti-inflammatory drugs on clinical and histologic features in celiac disease

Jordan

Shannahan

Lewis

et al. 2017

Digestive and Liver Disease

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Introduction The prevalence of celiac disease (CD) in the US has increased in past decades, as has use of proton pump inhibitors (PPIs), histamine-2-receptor antagonists (H2RAs), aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs). We aimed to measure the association between medication use and distribution of villous flattening (VF) among newly diagnosed CD patients. Methods We performed a cross-sectional study of adult patients with newly-diagnosed CD at two institutions. We collected data on regular use of these medications, clinical presentation, CD serologic status, and distribution of VF. We compared current ASA/NSAID users to non-users, and current PPI/H2RA users to non-users, with regard to these clinical characteristics. Results Of 148 patients with newly-diagnosed CD, current users of ASA/NSAIDs were older than non-users (47 vs 39 years, p=0.003) and users of PPI/H2RAs were older than non-users (48 vs 39 years, p=0.004). PPI/H2RA users comprised 12% of seropositive patients, compared to 55% of seronegative patients (p<0.01). Patient gender and distribution of villous flattening in the bulb and distal duodenum did not differ by PPI/H2RA or ASA/NSAID use. Conclusions PPI/H2RA use was associated with seronegative CD. Given the effect of these medications on gastric milieu, the impact of these drugs on presentation and course of CD deserves further investigation.

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Seronegative celiac disease: Shedding light on an obscure clinical entity

Abstract: Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders.

Cited by 89 publications

References 30 publications

Gamma delta⁺ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Gamma delta⁺ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Lymphocytic duodenitis or microscopic enteritis and gluten-related conditions: what needs to be explored?

The impact of acid suppression medications and non-steroidal anti-inflammatory drugs on clinical and histologic features in celiac disease

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Seronegative celiac disease: Shedding light on an obscure clinical entity

Abstract: Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders.

Cited by 89 publications

References 30 publications

Gamma delta+ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Gamma delta+ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Lymphocytic duodenitis or microscopic enteritis and gluten-related conditions: what needs to be explored?

The impact of acid suppression medications and non-steroidal anti-inflammatory drugs on clinical and histologic features in celiac disease

Contact Info

Product

Resources

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Gamma delta⁺ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

Gamma delta⁺ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy