Review Article

No-biopsy diagnostic approach to coeliac disease

Geoffrey K Holmes

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

This brief review outlines contributions that Michael Marsh and others made to understanding the structure and function of the upper small bowel mucosa and the formation of abnormalities that occur in coeliac disease (CD). He introduced his classification of lesions 30 years ago that has been widely adopted. The development and use of serological tests to screen for and diagnose CD in children and adults without the need for a small bowel biopsy in a considerable proportion is also recognised and will gain traction. 

The role of serology in the diagnosis of celiac disease

Umberto Volta, Julio Cesar Bai, Roberto De Giorgio

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era. Several markers for CD with a progressive diagnostic accuracy have been identified over the years, but only three of them, i.e. anti-tissue transglutaminase (anti-tTG), anti-endomysial (EmA) and anti-deamidated gliadin antibodies (DGP) are currently assessed in the daily clinical practice. A thorough review of the literature identified 44 original studies published between 1998 to 2022 for a total of 5098 pediatric and adult CD patients (without selective IgA deficiency) and 11930 disease controls. The results highlighted that anti-tTG IgA exhibited a higher sensitivity for CD (93.4%) than EmA IgA (92.8%), DGP IgG (81.8%) and DGP IgA (83.8%). The specificity of EmA IgA (99%) resulted to be higher than those of anti-tTG IgA (95.8%), DGP IgG (96.4%) and DGP IgA (92.1%). In patients with selective IgA deficiency, a condition closely related to CD, serological screening should include one of the three antibodies of IgG class, since anti-tTG, DGP and EmA have a very similar diagnostic accuracy in this clinical setting. According to age, there are two main diagnostic strategies for CD detection. In children, the revised ESPGHAN 2020 guidelines established that CD could be diagnosed in both symptomatic and asymptomatic children by high anti-tTG IgA titers (>10 times the cut-off) and EmA positivity with no need to obtain duodenal biopsy and HLA typing. In adult patients, although high tTG IgA titers (confirmed by EmA IgA positivity) correlate with villous atrophy, an intestinal biopsy is still considered mandatory for confirming CD diagnosis. Currently, a case finding approach in at-risk groups is preferred to mass screening for CD detection.

The correct methodological approach to the diagnosis of celiac disease: the point of view of the pathologist

Vincenzo Villanacci, Rachele Del Sordo, Giovanni Casella, Gabriel Becheanu, Arianna Oberti, Baraa Belfekih, Gabrio Bassotti, Alberto Ravelli

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

The diagnosis of celiac disease relies on the assessment of serological data and the presence of histological alterations in the duodenal mucosa.  The duodenal biopsy is pivotal in adults, and in some circumstances in children, to confirm the clinical suspicion of celiac disease. The correct interpretation of duodenal biopsies is influenced by numerous variables. The aim of this overview is to describe the correct methodological approach including the procedures of biopsy sampling, orientation, processing, staining and histopathological classification in order to avoid or minimize the errors and the variability in duodenal biopsy interpretation.Multiple biopsies taken from different sites of the duodenum during endoscopy maximize the diagnostic yield of duodenal histological sampling. Proper orientation of the biopsy samples is of the utmost importance to assess histological features of pathological duodenal mucosa and to avoid artifacts that may lead even an experienced pathologist to a wrong histological interpretation with subsequent misdiagnosis of celiac disease. An immunohistochemical stain for CD3 can be invaluable to aid the pathologist in obtaining a more accurate intra-epithelial T lymphocytes count. A simplified histological classification facilitates the clinician’s work and improves the communication between pathologist and clinician. An integrated clinical and pathological approach is required for a correct diagnosis of celiac disease since a relatively large number of conditions may cause duodenal damage with a histological appearance similar to that of celiac disease.

A substantial number of coeliac disease patients fail to respond to treatment with a gluten-free diet. Non-responsiveness might be multifactorial and the spectrum ranges from intentional or inadvertent gluten contamination as the main aetiology, to sensitivity to other nutrients (in addition to additives and preservatives). If the diagnosis of coeliac disease is correctly made and cross contamination and other factors have been excluded, then the aetiology behind the symptoms of a small group of coeliac patients might be refractory coeliac disease. The journey to ensure gluten contamination is not behind the persistent symptoms, is very challenging and requires in-depth training and skills. We therefore present potential guidance for the healthcare professional, in particular dietitians, on how to navigate these challenges on this journey.

Collagenous colitis associated with novel sprue-like intestinal diseases

Hugh James Freeman

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Almost a half-century ago, an unusual and distinct form of colitis was first recognized, collagenous colitis, characterized by sub-epithelial trichrome-positive deposits having the ultrastructural features of collagen. Later, other reports documented more extensive collagenous dis-ease in these patients, sometimes in the stomach and small bowel, a close linkage with other forms of microscopic colitis and its association with celiac and other immune-mediated diseases. Moreover, emerging genetic methods permitted large studies of collagenous colitis to complement these intriguing clinical and pathological studies.  Finally, recent and related studies have further demonstrated these immune-based forms of colitis, with new sprue-like intestinal diseases caused by novel medications, recently detected viral infections and vaccinations.    

Original Article

Relationship between anxiety and quality of life in the presence of other factors in adult celiac patients; a nationwide study

Yeganeh Sharifnejad, Farzaneh Amanpour, Kamran Rostami, Mostafa Rezaie Tavirani, Mohamad Amin Pourhoseingholi, Mohammad Rostami-Nejad

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: This study aimed to detect relationships among quality of life (QoL) and anxiety and demographic factors in patients with celiac disease (CD).

Background: CD is a type of autoimmune small intestine diseases caused by gluten ingestion. In Iran, the prevalence of CD is considered to be 1% in the general population. As physical problems and behavioral disorders of CD can lead to a reduction in QoL.

Methods: This cross-sectional study was performed on 533 patients with Celiac Disease from 9 cities of Iran. Data collected were analyzed by SPSS version 22. Quality of life and anxiety respectively evaluated by (GHQ-28) and SAS questionnaires. Predictors of quality of life (sex, age, age of diagnosis, city of life, education level, family history of celiac, occupation and anxiety) were tested by multiple linear regression.

Results: Our results showed a significant relationship between poor quality of life and anxiety (correlation= -0.143, P=0.001). The mean of the quality of life index in celiac diseases was 126.2±30.4 and women had a lower quality of life than men (P=0.003) importantly in emotions and worries scores. There was no significant difference between male and female in terms of anxiety level.

Conclusion: According to the results, both quality of life and anxiety correlated together and women seem to suffer more than men from celiac disease. Therefore, greater attention to women who have celiac disease are suggested.

Long-term follow-up in patients with coeliac disease in the pandemic-era: a view from Sheffield the NHS England national centre for adult coeliac disease

Nick Trott, Suneil A Raju , Dr Anupam Rej , Olivia Hoffman, William Holland, James R Bebb, Leah Seamark , Marianne Williams , Cristian Costas Batlle, Dr Yvonne M Jeanes, Luca Elli, David S Sanders

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: To explore patients follow-up preferences.

Background: Optimal follow-up strategies for patients with coeliac disease remain a subject of debate. Research suggests patients prefer review by dietitians with a doctor available as required.

Methods: Patients with coeliac disease under review at our centre, completed a questionnaire assessing their views on what makes follow-up useful based on specific criteria. Bloods tests, symptoms review, dietary assessment, opportunity to ask questions and reassurance. Patients preferences between follow-up with a hospital doctor, a hospital dietitian, a hospital dietitian with a doctor available, a general practitioner, no follow-up or access when needed were also evaluated.

Results: 138 adult patients completed the questionnaire, 80% of patients reported following a strict gluten free diet (mean diagnosis was 7.2 years). Overall, 60% found their follow-up to be ‘very useful’ valuing their review of blood tests and symptoms (71%) reassurance (60%) and opportunity to ask questions (58%). Follow-up by a dietitian with a doctor available was the most preferred option of review (p<0.001) except when compared to hospital doctor (p=0.75). Novel modalities of follow-up such as telephone and video reviews were regarded as of equal value to face-to-face appointments (65% and 62% respectively). Digital applications were significantly less preferable (38%, p<0.001).

Conclusion: Follow-up by a dietitian with a doctor available as needed was the most preferred follow-up method. However, in this study follow-up by a dietitian with doctor available and hospital doctor alone was statistically equivalent. Many patients consider telephone and video follow-up of equal value to face-to-face reviews.

Bone mineral density in Iranian children with celiac disease

Shokoufeh Ahmadipour , Mohamad Rostami nejad , Mojgan Faraji Goodarzi, Siroos Heidarifard , Banafsheh Sedaghat , Khatereh Anbari

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: The current study aims to evaluate bone mineral density (BMD) in patients with celiac disease who were referred to the celiac clinic of Shahid Rahimi Hospital in Khorramabad, Iran, in 2020.

Background: Extraintestinal presentations of celiac disease are widespread and, if neglected, can be devastating. Osteoporosis, one of the extraintestinal manifestations of celiac disease, often remains undiagnosed until advanced stages and can impose a significant burden on patients with celiac and health systems. Nonetheless, the prevalence and characteristics of osteoporosis in celiac disease are unknown in Iran.

Methods: This was a cross-sectional study at the celiac clinic of Shahid Rahimi Hospital in Khorramabad, Iran. Participants were 48 patients under 18 years diagnosed with Marsh II and Marsh III stages of celiac disease (who need to be on a gluten-free diet) at the pediatrics celiac clinic in 2020. All patients were recruited, completed a questionnaire, and had their blood biochemical parameters analyzed. Then their bone mineral density (BMD) was measured through dual-energy x-ray absorptiometry at the Asia Imaging Center in Khorramabad under the supervision of a radiologist and pediatric rheumatologist.

Results: The mean age of the children was 9.96±3.17 years. The minimum and maximum ages of the participants were 4 and 17 years, respectively. Of all 48 children who were included (48), 34 (70.8%) were female, and 14 (29.2%) were male. In the femoral region bone densitometry, 35.4% were normal, 41.7% had lower limit normal, and 22.9% had low bone density. In the lumbar region, 39.6% were normal, 25% were Lower limit normal, and 35.4% had low bone density. No significant correlation was found between age, sex, place of residence, Marsh stage, gluten-free diet, and bone densitometry in both lumbar and femoral regions. Nonetheless, we detected a statistically significant relationship between bone density in the lumbar region and two HLA types, namely HLA DQ8 and HLA DQ2/8 (PV=0.016).

Conclusion: The results of the current study provided further evidence that all children with advanced celiac disease should be screened for metabolic bone diseases. Besides those in Marsh II and Marsh III, patients in Marsh I stage should also be investigated for low bone mineral density.

Aim: The aim of this work was to highlight the impact and hidden costs incurred by the NHS in supporting this management process.

Background: Coeliac disease (CD) is a common auto-immune condition which affects around 1% of the general population. In 2005 there was a drive by the government to discharge patients with CD from specialist hospital follow up to community-based management to improve cost efficiency.

Methods: A retrospective analysis of 1317 CD patients collected from a local coeliac database created between 2005–2016.

Results: During these 12 years, CD patients accounted for 1965 hospital admissions with a total 5716 days spent within the hospital setting. There were 33150 adult and paediatric OPAs attended equating to 25.17 per coeliac patient, or 2.29 per person per year. The cost to the CCG totalled £5,167,396. A total of 527 lower GI procedures were undertaken with findings of microscopic colitis, melanosis coli, inflammatory bowel disease and colon cancer. 420 (29%) of the coeliac cohort were found to have IDA with just 4% (17/420) receiving an intravenous (IV) iron infusion.

Conclusion: It would appear that the government’s attempts to reduce the cost of CD care within the NHS was not particularly effective, from a financial, or patient care perspective. A hospital-based, specialist nurse led, virtual management system (with consultant over-view) may prove to be a more efficient compromise, to help reduce down waiting times and costs, whilst still providing coeliac patients with the specialist and holistic input they require and deserve.

The differential diagnoses for severely damaged small intestinal mucosa

Chao Ling Aran Jian, David T. S. Hayman, Bruce Lockett, Kamran Rostami

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: The aim of this study was to explore the aetiology of severe duodenal mucosal abnormality in consecutive patients who underwent gastroscopy and duodenal biopsy over the past 10 years.

Background: A range of differential diagnoses have been reported for severe duodenal architectural distortion.

Methods: Clinical and laboratory data of all the patients with severe duodenal architectural distortion diagnosed at MidCentral District Health Board (DHB), New Zealand were collected and statistically analysed. Ninety-five percent confidence intervals (CI) are shown.

Results: Between September 2009 and April 2019, 229 patients were diagnosed with severe enteropathy. The median patient age was 41 years (range 6-83 years). Two hundred and twenty-four of these patients (97.8%, 95.0-99.3%) were diagnosed with coeliac disease (CeD), with one of these patients having gluten induced T-cell lymphoma. From the remaining five patients, one had a diagnosis of tropical sprue and four did not have a clear aetiology. There were 180 patients from 191 (94.2%, 89.9-97.1%) with at least one positive coeliac marker, all with a diagnosis of CeD. Eleven patients (5.8% of 191, 2.9-10.1%) had negative markers for both tissue transglutaminase IgA (tTG-IgA) and IgA-endomysial antibodies (EMA-IgA) with six having a diagnosis of seronegative CeD.

Conclusion: Although the spectrum of histological changes in CeD may range from normal to a flat mucosa, severe duodenal architectural distortion seems to occur mainly in CeD. Idiopathic enteropathy was recorded as the second but by far less frequent presentation of severe enteropathy. This study highlights that infection and other aetiologies are rarely implicated in severe enteropathy, with one case (0.4%) of refractory CeD/T-cell lymphoma.

Celiac disease: experience of general practitioners in Brianza Area- Monza- Milan-Italy

giovanni casella, maria teresa bardella, fabio ingravalle, adriana ingravalle, stefano andreotti, aurelio limonta, claudio monti, vincenzo villanacci, gabrio bassotti

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: The purpose of the study was to better investigate the degree of knowledge and the diagnostic approach concerning celiac disease and its extra-intestinal manifestations by general practitioners in Italy.

Background: Celiac Disease is a common chronic disease, but often goes undiagnosed because of atypical symptoms or silent disease. Currently there are non-definitive data about the disease management approach concerning celiac disease by general practitioners.

Methods: To better investigate the degree of knowledge and the diagnostic approach concerning celiac disease and its extra-intestinal manifestations, questionnaire was used to assess the daily practice of diagnosis, treatment, and follow-up of this condition by general practitioners in two densely populated area in Italy: Monza-Brianza Area and Milan City. The questionnaire was composed of 18 questions that explored 3 precise domains: diagnosis criteria, correct management of celiac disease and availability for training. The frequencies of the domains explored were analyzed, analyzes were carried out to identify differences between the groups of general practitioners interviewed.

Results: Analysis of the questionnaires showed a degree of knowledge and preparation comparable to that of other countries, even though not sufficient to guarantee access to early diagnosis for all patients with celiac disease. The knowledge was not influenced by the years of experience or specific curriculum of health professionals. General practitioners under 40 were much more in favor of continuous training and were aware of its importance (OR=10.55; CI95 1.62-445.39), although this need was a high priority in the whole group interviewed (84.7%).

Conclusion: Continuous specific training aimed at primary care physicians and general practitioners is the first tool to improve early diagnosis. A second opportunity is represented by the continuous dialogue between general practitioners and tertiary level hospitals and universities.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease


Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD).

Background: Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment.

Methods: The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016-2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis.

Results: A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR.

Conclusion: Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Clinical profile of patients with seronegative celiac disease

Elham Rahmanipour, Mohammad Ghorbani, Azita Ganji, Zahra Mirzaei, Vahid Ghavami, Bijan Shahbazkhani, Fahime Attarian, Masoumeh Amiri

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: This study aimed to determine the clinical profile of patients with seronegative celiac disease (SNCD).

Background: Celiac disease (CD) is mainly diagnosed based on positive serology and duodenal mucosal atrophy, but some patients have negative serology. Their diagnosis has some limitations; delays in diagnosis are likely accompanied by a poor prognosis and a high risk of developing complications of CD.

Methods: In this retrospective study, 1115 patients were evaluated for CD with mucosal atrophy between 2010 to 2020. SNCD diagnosis requires genetic CD predisposition and improvement of both clinical symptoms and regrowth of duodenal villi after 12 months of a gluten-free diet (GFD) for all patients with IgA deficiency, other IgG-based serology for diagnosis of celiac was done and if these antibodies were negative, consider them as possible SNCD. If they had positive DQ2-DQ8 and improvement of clinical symptoms and mucosal atrophy after 12 months of GFD were confirmed SNCD.

Results: Of the 1115 study subjects, 27 had SNCD, 1088 had SPCD with a mean age of 29.7±15.7 years (1 to 76 years) in seropositive celiac disease (SPCD) subjects and 37.1±16.3 years (6 to 63 years) in SNCD participants and 19 female patients with SNCD were presented. The BMI of SNCD and SPCD patients were reported 23.9 and 21.4, respectively. In addition, SPCD subjects were more likely but not statistically significant to have a positive family history. Villous atrophy was shown in 100% SNCD and 95.6% SPCD cases. Scalloping and fissuring in duodenal biopsies were reported in 60% of SNCD and 84.5% of SPCD patients. There was some other cause of seronegative villous atrophy including 3 patients with Crohns disease, 2 with common variable immunodeficiency, 2 drug and one patient with peptic duodenitis. Anemia, neurological symptoms, and liver function tests (LFT) abnormality were common extra intestinal manifestations in SNCD individuals. Levels of Thyroid peroxidase (TPO), TSH were measured, it had been detected that SNCD cases had a higher rate of co-occurrence with thyroid diseases also SPCD cases showed a higher rate of co-occurrence with diabetes.

Conclusion: Among patients with celiac disease 2.4% are SNCD. SNCD are older than SPCD at the time of diagnosis and have higher BMI. Most common of cause of seronegative enteropathy also is SNCD followed by inflammatory bowel disease (IBD) common variable immunodeficiency (CVID), medication use, and duodenitis, in this area.

Is Irritable Bowel Syndrome out of date and misleading as a diagnosis?

Taliah Sua, Carlos Montoya, Dongwen Luo, Kamran Rostami

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: This study aimed at assessing the efficacy of targeted interventions addressing common food sensitivities and lifestyle factors that commonly contribute to the presentation of gastrointestinal problems identified as Irritable bowel syndrome (IBS).

Background: IBS has served to cover the expression of multifactorial disorders with variable aetiology and pathophysiology. Food antigens implicated in the modern lifestyle, acting as strong epigenetic factors is strongly implicated in pathophysiology of conditions under IBS. Identifying and addressing food sensitivities in patients presenting with IBS like symptoms are currently underemphasised in clinical guidelines yet have the potential to provide major benefits for patients.  

Methods: Information was collected from the medical records of patients that were referred to the Gastroenterology Unit of Palmerston North DHB with unexplained gastrointestinal (GI) symptoms with or without other GI comorbidities between September 2018 and November 2021.

Results: The main management option offered to the 121 patients included in this study, was lifestyle adjustment and/or a trial of 6 weeks, eliminating gluten and lactose from the diet. The most prevalent symptoms were abdominal pain 96/121 (79%), diarrhoea 83/121 (69%), followed by bloating and constipation. Seventy-eight patients had the outcomes of their improvement available. A total of 42 out of 78 patients (54%) were treated exclusively with gluten and lactose-free diet, in this group of patients 86% (36/42) reported a significant improvement in their symptoms with a score in the range of 40-100%.

Conclusion: Our study illustrates the importance of focusing on triggering factors when assessing patients with IBS. We suggest that careful identifying and eliminating the triggering food antigens as monotherapy or in addition to the lifestyle adjustment where appropriate should be the main objective in symptomatic patients fulfilling the IBS diagnostic criteria. These combinations and holistic approach in treating IBS’ patients’ symptoms are less expensive, non-toxic, and highly effective in achieving optimal outcomes and improving these patient’s quality of life.

Brief Report

Assessment of iron status and iron deficiency anemia in patients with celiac, a single center experience

Seyyed Ali Pirzadeh, Taghi Amiriani, Sima Besharat, Alireza Norouzi, Haniyeh Mirkarimi, Nesa Shokouhifar, Gholamreza Roshandel, Amrollah Sharifi

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Aim: This study aimed to assess the status of iron stores and the frequency of iron deficiency anemia in Celiac disease (CD) patients referred to the Golestan Research Center of Gastroenterology and Hepatology, Gorgan, Iran.

Background: Studies have shown that nutritional deficiencies affect 20-38% of patients with CD due to malabsorption and as a result of a gluten-free diet.

Methods: In this study, 59 out of 100 CD patients were assessed. The presence and severity of anemia were determined using the concentration of serum hemoglobin according to WHO criteria. The status of body iron stores was also assessed based on serum ferritin levels.

Results: Mean and SD of age, duration of disease, serum hemoglobin, ferritin, TIBC, and serum iron were 39.9±11.9 years, 69.8±45.4 months, 12.6±1.99 g/dl, 54.3±55.3 mg/dL, 365.9±49.1 μg/dL, and 84.1±37.1 μg/dL, respectively. 68.42% had no anemia, 19.3% had mild anemia, 8.77% had moderate anemia, and 3.51% had severe anemia. 25.42% of patients had depleted iron stores, 71.19% had normal iron stores, and 3.39% were exposed to iron overload. There was a statistically significant correlation between serum hemoglobin and the duration of disease diagnosis (P=0.037, r=0.302).

Conclusion: In this study, 31.58% of CD patients on a gluten-free diet had some degree of anemia. In addition, 25.42% of patients had depleted iron stores. These results suggest that CD patients should be evaluated for iron status, even with a gluten-free diet.

Case Report

Transient Non-coeliac gluten sensitivity with markedly reduced villous height/crypt depth

Charlotte Williams, Nicole Smith, Kamran Rostami

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

There is no confident evidence in the current literature to show or demonstrate that non-coeliac gluten sensitivity (NCGS) exclusively presents with mild or nearly normal duodenal mucosal abnormality. Gluten sensitive patients with negative serology and severe mucosal changes are labelled with the term seronegative coeliac disease (SNCS). There might be at least some overlap between NCGS and SNCD. Transient gluten sensitivity with severe mucosal changes without CD have been previously reported like in our case.

Tufting enteropathy: a rare anatomical cause of small bowel diarrhoea in infants with mild or no villous abnormality

PRASENJIT DAS, Rohan Malik, Sanjeevani Kaul, Govind Makharia

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

The causes of intractable diarrhoea in infancy are varied, and can be classified into enteropathic and non-enteropathic groups. Congenital tufting enteropathy (CTE) is a rare cause of enteropathic form of intractable diarrhoea in infants requiring nutritional supplementation. We herein report a case of CTE in a one-year-old female child who presented with recurrent abdominal distension, frequent watery diarrhoea and marked stunted growth soon after birth. A systematic clinical, laboratory and pathological evaluation brought out the etiology, followed by genotypic confirmation. Histological examination revealed mild villous abnormality with presence of epithelial tufts both in the villous and crypt surface, in the duodenum and rectal biopsies supported by complete loss of MOC31 staining. Deep sequencing revealed homozygous 3’ splice mutation at intron 5 of the EPCAM gene (c.556-14A>G). She was given TPN support and discharged with weight gain under home-based parenteral nutrition supplement. This case brings out the need for a multidisciplinary team approach to reveal underlying the cause of infantile intractable diarrhoea and report a favorable outcome with nutritional supplementation.

What does not look like celiac disease and instead it is

Vincenzo Villanacci, Rachele Del Sordo, Orsola Setti, Barbara Zanini, Giovanni Casella

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

The celiac disease (CD) diagnosis sometimes is challenging and diagnostic process cannot always follow a simple algorithm but it requires a close collaboration between histo-pathologists, clinicians, laboratory and genetic experts. The genetic predisposition for CD is related to HLA-DQ2 and/or DQ8 but other HLA haplotypes and non-HLA genes may be involved in genetic predisposition. In particular DQ7 may represent an additive and independent CD risk associated haplotype. We describe an unusual case of a female 42 year old with a previous diagnosis of Hodgkin lymphoma, who has a clinical presentation suggestive for CD with negativity for anti-transglutaminase and anti-endomysium antibodies and HLA-DQ7 positivity.

Not all enteropathies are coeliac disease! Report of an infant with microvillus inclusion disease

Eda Nur Kozan, Ceyda Tuna Kırsaçlıoğlu, Zarife Kuloğlu, Aydan Kansu, Berna Savas, Arzu Ensari

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

Primary enteropathies of infancy comprise of epithelial defects including microvillus inclusion disease, tufting enteropathy, and enteroendocrine cell dysgenesis and autoimmune enteropathies. The diseases in this group cause severe chronic (>2-3 weeks) diarrhoea starting in the first weeks of life and resulting in failure to thrive in the infant. Duodenal biopsies show moderate villous shortening together with crypt hyperplasia which are the main features causing resemblance to coeliac disease.

We, hereby, report a term-born male infant of consanguineous parents. His two siblings died during infancy. He developed watery, urine-like diarrhea on the 3rd day of his life. On the postnatal 6th day he weighed 2750 grams, became dehydrated and had metabolic acidosis. Upper GI endoscopy performed on the postnatal 20th day appeared normal. Light microscopic examination of the duodenal biopsy showed moderate villous blunting, with mildly increased inflammatory cells in the lamina propria or and intraepithelial lymphocytosis. Enterocytes at the villous tips showed an irregular vacuolated appearance in the apical cytoplasm with patchy absence of the brush border demonstared by PAS and CD10. Electron microscopy revealed intracytoplasmic inclusions that were lined by intact microvilli in the apical cytoplasm of enterocytes. As he was dependent on TPN and aggressive intravenous fluid replacement he was hospitalized throughout his life. He died when he was 3 years and 4 months old.

Paediatric coeliac disease is in the differential diagnosis of primary enteropathies of childhood. The differentiation lies on duodenal biopsy interpretation together with genetic analysis to detect the underlying genetic defect in childhood enteropathies.

Immune checkpoint inhibitor therapy associated enteritis mimicking celiac disease

Binny Khandakar, Amitabh Srivastava

Gastroenterology and Hepatology from Bed to Bench, Vol. 16 No. 2 (2023), 21 April 2023,

A 68-year-old man with a previous history of lung cancer presented with deteriorating appetite and weight loss. Imaging revealed significant retroperitoneal lymphadenopathy, as well as liver and bone lesions consistent with widespread metastatic carcinoma. Biopsy results from the liver lesions confirmed the diagnosis of metastatic non-small cell lung carcinoma. A PDL-1 immunostain, performed on the initial lung resection specimen, showed a combined positive score (CPS) of 15 and pembrolizumab treatment was initiated. The patient presented with diarrhea three weeks after starting therapy and duodenal biopsies obtained at this time displayed intact villous architecture with an increase in intraepithelial lymphocytes (IELs). The colon biopsies exhibited lymphocytic colitis, characterized by significant thinning of the surface epithelium, a higher mixed inflammatory infiltrate within the lamina propria, and diffuse increase of IELs (greater than 30 per 100 epithelial cells). These findings collectively raised the differential diagnosis of celiac disease with lymphocytic colitis or immunotherapy-associated enterocolitis. Further serological testing for celiac disease, including anti-tissue transglutaminase antibodies, yielded negative results. Consequently, a final diagnosis of immune adverse event associated with immunotherapy was established. Cases reported in literature as celiac disease occurring soon after immunotherapy are likely misdiagnosed cases of immunotherapy enteritis.