Lymphocytic Duodenosis Research Articles

Effect of Esophagogastroduodenoscopy Volume and Gastric/Esophageal Pathology on the Rate of Lymphocytic Duodenosis Reporting in Children and Adolescents.

Background It is not clear if the increase in the number of esophagogastroduodenoscopies (EGDs) performed has any significant effect on the rate of lymphocytic duodenosis (LD) reporting in children and adolescents and whether it correlates with abnormal gastric and/or esophageal pathology." Methods We performed a single-center retrospective study using the Mayo Clinic electronic health record and pathology database. We reviewed all EGD procedures performed in children and adolescents (<18 years) between January 1, 2000, and December 31, 2018, and identified two groups, the LD group and matched age and sex control group (normal duodenal biopsies). We evaluated the correlation of LD rate with the yearly number of EGDs performed and the presence of abnormal gastric and/or esophageal pathology. Results Of 11,870 EGDs performed, we identified 338 (3%) individuals with LD and 390 (3%) randomly selected controls, with a mean (SD) age of 9.6 (5.3) and 11.7 (5.0) years, respectively. Based on logistic regression analysis, abnormal gastric histology was associated with the presence of LD when compared with controls (odds ratio, 2.85; 95% CI, 2.05-3.97; P < 0.001). The rate of LD-positive biopsies per year was highly correlated with the number of EGDs performed (ρ = 0.931; 95% CI, 0.826-0.974; P < 0.001). Conclusion The rate of LD reporting is correlated with the number of EGDs performed and is more likely seen in children and adolescents with abnormal gastric histology.

The Significance and Clinical Outcome of Lymphocytic Duodenosis in Children: Mayo Clinic Experience and Systematic Review.

Lymphocytic duodenosis (LD) defined as increased intraepithelial lymphocytes >25 intraepithelial lymphocytes (IELs) per 100 epithelial cells with normal villous architecture is associated with many gastrointestinal (GI) disorders. We aim to assess the rate and outcome of LD in children and perform a systematic review. We reviewed all children (<18 years) who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsy between January 2000 and June 2019 to identify LD cases and control group. Demographics, clinical, and pathologic information were reviewed and recorded. A systematic review including our findings was performed. During the study period 12,744 children underwent an EGD with biopsies. Of those, we identified 426 children with LD (3%) and 474 controls. The median age in years was 10.7 and 12.6 and there were 254 (60%) and 278 (59%) girls in the LD and control group, respectively. The most common presenting symptoms in both groups were abdominal pain (52%), gastroesophageal acid reflux disease (18%), diarrhea (16%), and vomiting (12%). Diarrhea (21% vs 12%, P < 0.001) and constipation (2% vs 0.4%, P = 0.021) were statistically different between the LD and control group, respectively. Median follow-up (range) is 3.6 (0.0, 190.9) and 3.1 (0.0, 194.2) in the LD and control group, respectively. CD (5% vs 0%, P < 0.001), Crohn disease (9% vs 3%, P = 0.003) and Helicobacter pylori gastritis (3% vs 1%, P = 0.021) were more common in the LD group. The Rate of LD in children is similar to reported rate in adults. In the absence of Crohn disease, CD or H. Pylori, LD seems to be a benign and transient histologic finding in children.

Elevated Serum Tissue Transglutaminase Antibodies in Children With Eosinophilic Esophagitis.

This study compared the clinical and histopathological characteristics of children with eosinophilic esophagitis (EoE) and elevated anti-transglutaminase (TTG Ab) with those with EoE and normal TTG Ab titres. Single-center chart and blinded histopathological review of patients diagnosed with EoE for a 4-year period, who had esophageal and duodenal biopsies taken at time of endoscopy, and TTG Ab measured within 6 months of biopsy. Patients with histology-proven CD were excluded. Elevated TTG Ab was present in 19/34 (54%) of the study cohort, representing 23% of all patients diagnosed with EoE during the study period. Eight had titers >6× upper limit of normal (ULN) and 4 had >10× ULN. TTG Ab-positive patients were classified as having either potential CD with (n = 3, 16%) and without lymphocytic duodenosis (LD; n = 12, 63%), and no CD (n = 4, 21%) on human leukocyte antigen typing. There was an increase in duodenal eosinophils in patients with elevated TTG Ab (P = 0.01), which remained when patients with LD were excluded (P = 0.018). Of 19 patients with EoE and elevated TTG Ab, 5 responded to elimination diet involving exclusion of wheat, including 2 with a sole wheat trigger and TTG Ab >10× ULN that were CD-associated human leukocyte antigen-negative. Serum TTG Ab was elevated in almost one-quarter of our total EoE cohort, and at least 20% of these patients did not have potential CD, suggesting EoE is a heterogeneous disease with differing immune mechanisms activated in some patients. These findings also support routine esophageal biopsy during upper endoscopy in children with elevated TTG Ab.

Duodenal Villous Blunting: Hint for Underlying Malignancy

Introduction: The characteristic changes found during small intestinal remodeling in celiac disease include inflammatory villous blunting or atrophy. Villous blunting with sero-negativity for celiac disease is a diagnostic and therapeutic challenge. Case Description: 66 years old woman was referred to our clinic for the evaluation of chronic diarrhea, unintentional weight loss and malabsorption. She had a history of vitamin B12 deficiency, peripheral neuropathy and frequent falls leading to subdural hematomas. She had tried gluten free diet for a few months without improvement. Laboratory investigations including CBC, CMP, lipase, albumin, Iron, Folate, prothrombin time, vitamin B1, B6, B12 and D were within normal limits. Work up of celiac disease including IgA and IgG Tissue transglutaminase and gliadin peptide were negative. Her intrinsic factor blocking antibody was negative. Biopsies of the duodenal mucosa revealed focal chronic inflammation with villous blunting (Figure 1) which was not pathognomonic for Celiac disease. She was found to be HQ2/HQ8 negative. Magnetic Resonance Enterography (MRE) showed a right ovarian cystic carcinoma with metastatic lymphadenopathy without any bowel inflammation.She was treated by bilateral salphingo- oophorectomy and total hysterectomy, followed by chemotherapy. Discussion: Villous atrophy of the small intestine mucosa occurs most commonly in Celiac disease.The histological changes in celiac disease are best defined by the Modified Marsh classification (Table-1). Villous atrophy (VA) associated with malignancy is infrequently seen and reported. Creamer et al have reported 6 cases of extra intestinal solid malignancies causing villous atrophy. Local tumor infiltration with CD4+ cells and increased production of Th1 cytokines and interferon gamma leads to oligoclonal expansion of CD4+ helper T cells as an antitumor response. Tumor specific T cells can be found to circulate in 50 % of patients with ovarian carcinoma. The small intestine can be affected by this activation of CD4+ T helper 1 cells leading to intraepithelial lymphocytosis (lymphocytic duodenosis) and features of villous atrophy and crypt hyperplasia without gluten hypersensitivity. Conclusion: Villous atrophy without celiac disease can occur in underlying extra intestinal malignancies like ovarian cancer leading to diarrhea, malabsorption and weight loss. Sero- negative celiac disease with villous atrophy should be evaluated for underlying malignancy.Figure 1Table 1: Modified Marsh Classification of Small intestinal changes

OC-028 Does Duodenal Histology Yield any Other Diagnoses for Iron Deficiency Anaemia Apart From Coeliac Disease?: Abstract OC-028 Table 1

Introduction The prevalence of iron deficiency anaemia (IDA) is 2–5% in the developed world. The BSG IDA guidelines recommend screening for coeliac disease (CD) with serology, and those tested positive should undergo duodenal biopsy to assess for villous atrophy (VA). The availability of pre-endoscopy serology in IDA has been shown to be 30%, thus often committing clinicians to routinely biopsy the duodenum. We aimed to explore whether any causes other than CD would be found on duodenal biopsy in IDA. We also aimed to evaluate the role of Simtomax, an IgA/G-deamidated gliadin peptide based point of care test (POCT), in detecting CD in IDA in the endoscopy setting. Methods Group 1: we retrospectively reviewed the duodenal histology of 153 patients with IDA attending a non coeliac specialised IDA clinic in 2013–14. Group 2: we prospectively recruited 133 patients with iron deficiency attending for a gastroscopy to our research gastroscopy list. All patients undertook Simtomax, endomysial antibodies (EMA), tissue transglutaminase (TTG), total IgA, and 5 duodenal biopsies. The results were compared against histology. Results The duodenal histology in group 1 yielded no cause for the IDA apart from CD. Two patients had VA- 1 with positive serology and hence was diagnosed with CD; the other patient never had a serology to confirm the diagnosis as he subsequently died from colon cancer. Assuming the latter case to be CD, the prevalence of CD in this cohort would be 1.3%. 5/7 patients with lymphocytic duodenosis (LD) had a cause for or association with LD: vitiligo, autoimmune hypothyroidism, aspirin use, proton pump inhibitor use, and Helicobacter pylori infection respectively. No attributable causes for LD were found in the remaining 2 patients. In group 2, the prevalence of CD was 19.5%. The sensitivity and NPV of Simtomax were 100%. Conclusion Our duodenal histology review revealed no alternative causes for the IDA other than villous atrophy secondary to CD. Simtomax had 100% sensitivity and NPV for detecting CD in IDA. This suggests that performing a duodenal biopsy in patients with a negative Simtomax test is highly unlikely to yield a diagnosis for IDA, thus could be safely avoided if the sole purpose of the biopsy is to investigate IDA. Simtomax could provide significant cost savings by targeting patients with IDA who require a duodenal biopsy. Disclosure of Interest M. Lau: None Declared, P. Mooney: None Declared, W. White: None Declared, M. Burden: None Declared, S. Wong: None Declared, M. Kurien: None Declared, S. Cross: None Declared, J. Hebden: None Declared, D. Sanders Grant/research support from: Tillotts Pharma for investigator led studies in coeliac disease. None of the funding sources had any input in the study design, access to study data, interpretation of the findings or drafting of the abstract.

Histopathology diagnosis of coeliac disease - clinicopathological correlation is key!

To The Editor: A robust diagnosis of coeliac disease is paramount for patient and clinician. The recent paper and subsequent editorial in this journal emphasises this point (1,2). However there is little mention of recent evidence based international guidelines in considering which classifications to use (3-5). These guidelines are carefully considered by the authors, have undergone rigorous review and are backed by the literature and outline both definitions of coeliac disease (3) and guidelines for diagnosis and management (4, 5). Why is it so important to make a cast iron diagnosis in coeliac disease? For the patient, treatment with a gluten free diet is costly, socially restricting and difficult, as many foods may have hidden gluten. For the clinician, the responsibility lies in prevention of future complications, ranging from the consequences of malabsorption such as osteoporosis to a possible malignant outcome. It is important that histopathologists, in tandem with clinicians, make an early diagnosis. For histopathology the difficulties often lie in making this diagnosis at an early stage. Two studies underline the importance of suggesting coeliac disease when the histopathological features do not include flat mucosa (6, 7). Patients with mild enteropathy may experience clear gluten-induced symptoms and benefit from a gluten free diet (6) and also have weight loss, anaemia, folate deficiency, hyperparathyroidism and evidence of osteoporosis (7). Aside from performing serology (and where needed HLA testing), endoscopists should take enough biopsies to allow us to make the diagnosis – at least 4-6, including duodenal bulb – to make a diagnosis as this increases the chance to spot early and histological features(8). We should also be mindful that normal architecture and ≥25 IELs/ 100 enterocytes (lymphocytic duodenosis (4) can represent coeliac disease in some patients, given the right clinico-pathological setting. Histopathologists should suggest this diagnosis when there is no current serology / HLA typing available to prompt these inveatigations. Although many other conditions are associated with LD (4,9), we must not ignore this finding. Mild enteropathy is not mild disease!

Does gluten free diet have more implications than treatment of celiac disease?

This study was aimed to evaluate symptomatic as well as histopathologic response to GFD in patients with gluten-sensitive enteropathies including celiac disease, lymphocytic duodenosis and non-specific duodenitis. Gluten-free diet (GFD) is the main treatment of celiac disease. However, its impact on other disorders of gluten sensitivity spectrum is less clear. In a prospective observational study in Modarres hospital Tehran, Iran, 35 patients with chronic manifestations including low BMI, diarrhea, greasy stool and bloating were evaluated using serology for anti-tTG, endoscopy and histopathology. Patients were categorized in three diagnostic groups accordingly including celiac disease (CD), lymphocytic doudenosis (LD) and non-specific duodenitis (NSD). All patients were put on a GFD for 6 months, and subjective symptomatic response, serology, endoscopy and histopathologic tests were repeated and compared with baselines and among groups. Of the total 35 patients, 5 had CD (14.3%), 9 had LD (25.7%) and 21 (60%) had NSD. Bloating was the most common symptom followed by diarrhea. Majority of patients (80%) had low BMI. All symptoms alleviated following a GFD but bloating was the only significant one. A significant increase was found in total mean BMI (17.3±0.7 v.s. 17.9±0.9). Histopathologic examination showed a complete resolution in 48.5% (n=17) patients, 10 in NSD group, 4 in LD group and 3 in CD group. Final prevalence of gluten-sensitive enteropathy (LD and NSD cases that responded to GFD) was 46.6%. GFD may have more implications other than celiac disease. Other gluten-sensitive enteropathies, like LD and NSD, might also respond to this treatment particularly in patients with low BMI.

Clinical expression of lymphocytic duodenosis in “mild enteropathy” celiac disease and in functional gastrointestinal syndromes

Objective. Abnormally high number of duodenal intraepithelial lymphocytes is frequently found in many conditions including mild enteropathy celiac disease (CD) and functional gastrointestinal syndromes, but is unclear whether lymphocytosis affects the clinical phenotype particularly in functional syndromes. Materials and methods. We compared clinical characteristics of celiac patients with lymphocytic duodenosis and normal villous structure with those of patients with functional gastrointestinal syndromes with and without lymphocytic duodenosis. We retrospectively identified 3 cohorts among patients referred for suspected CD: (1) “CoelD”, 135 patients (age 36 ± 14 years) with mild enteropathy CD; (2) “LymD”, 245 patients (38 ± 12 years) with functional gastrointestinal syndromes and lymphocytic duodenosis; and (3) “NorD”, 147 patients (37 ± 15 years) with functional syndromes and normal duodenal histology. Results. Prevalence of gastrointestinal symptoms was similar in the three cohorts, but prevalence of extra-intestinal manifestations (42% vs. 27% vs. 18%, p < 0.003) and of associated diseases (35% vs. 15% vs. 14%, p < 0.0001) was higher in “CoelD” than in “LymD” and “NorD”, respectively. Prevalence of Helicobacter pylori infection was similar in the three cohorts. The proportion of patients with final diagnosis of irritable bowel syndrome-diarrhea (38% vs. 37%), dyspepsia (31% vs. 27%), functional pain (14% vs. 19%), and functional diarrhoea (14% vs. 11%) was virtually the same in the cohorts with (LymD) and without (NorD) lymphocytic duodenosis. Conclusions. Lymphocytic duodenosis has different clinical presentation in patients with mild enteropathy CD than those with functional gastrointestinal syndromes, and is not specific for any particular functional syndrome.

OC-033 Is Lymphocytic Duodenosis a Marker for Irritable Bowel Syndrome?

Introduction Lymphocytic duodenosis (LD) is defined by normal villous architecture and intraepithelial lymphocytes (IELs) > 25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease (CD), solely by histology, as recent studies have suggested other associations with LD. Despite a paucity of data, previous investigators have suggested that LD may also be associated with irritable bowel syndrome (IBS). Aims To prospectively assess the associations between LD and IBS. Methods Two hundred patients with LD were investigated for associated LD conditions, by means of revisiting the patient’s history and recent investigations including the initial coeliac serology, followed by a combination of gluten challenge, HLA typing, repeat duodenal biopsies, and exclusion of infection/inflammatory bowel disease. A diagnosis of CD was based on the persistence or progression of LD on a gluten-containing diet, the presence of HLA DQ2 or DQ8, and a clinical response to a gluten free diet. In the absence of an alternative cause, a diagnosis of IBS was made on the presence of the ROME III criteria. Results 150 female, 50 male, mean age 49, SD 16, age range 17–83 An identifiable association was found in 70% of patients : CD (20%), NSAIDs (17%) and H.pylori (16%) accounting for the majority. Other causes included gastrointestinal infections (7%), autoimmune disorders (5.5%), inflammatory bowel disease (2%), TB or HIV (1.5%), and IgA deficiency (1%). In 60 cases (30%) no cause was found, although reassuringly two-thirds normalised their histology. In just over half of those without an identifiable cause, symptoms were consistent with IBS (35/60). IBS, therefore, accounted for 17% of all LD cases. Whereas all patients with CD were HLA positive, only 55% of those with alternative causes or IBS were HLA positive (p Conclusion 17% of LD is associated with the Rome III criteria for IBS. LD may, therefore, be a disease marker for IBS and a reflection of low grade inflammatory response although no clues to the triggering mechanism were elucidated. Disclosure of Interest None Declared

PTH-183 The Diagnostic Utility of Endoscopic Duodenal Biopsies for Gastrointestinal Investigation

IntroductionDuodenal biopsies are usually taken at upper gastrointestinal endoscopy to exclude coeliac disease (CD). To date, few studies have investigated overall duodenal pathologies in this group. Serological testing for anti-tissue...

Sa1287 Investigations for Coeliac Disease in Iron Deficiency Anaemia - Are We Following BSG Guidelines?

Introduction BSG guidelines for the investigation of iron deficiency anaemia (2011)1 recommend screening of these patients for coeliac disease (CD) by serology. Small bowel biopsy is recommended at OGD if coeliac serology is positive or not available. If coeliac serology is negative, small bowel biopsies need not be performed at OGD unless there is a high degree of suspicion for CD despite negative serology. Methods We retrospectively evaluated the use of coeliac serology testing (tissue transglutaminase antibody, tTG) and upper gastrointestinal endoscopy (OGD) with duodenal biopsies in the evaluation of anaemia, according to BSG guidelines in our NW London teaching hospital cohort. All upper GI endoscopies performed for anaemia over a 6-month period were reviewed for rates of duodenal biopsy and results, and serological testing. Results In 6 months, 206 OGDs were performed for anaemia. Duodenal biopsies were taken in 134/206 (65%). Of 72 (35%) procedures at which no duodenal biopsy was taken, another cause for anaemia found on OGD in 27, six had melaena or acutely falling haemoglobin as an indication for OGD, six had previous duodenal biopsies, and the procedure could not be completed in nine cases. Five patients with no duodenal biopsy taken at endoscopy had negative coeliac serology prior to OGD. 19/206 (9.2%) patients did not have duodenal biopsies taken at endoscopy, despite an indication for biopsy. 48/206 (23.3%) patients referred for an OGD with anaemia had coeliac serology performed (34 prior to OGD and 14 after OGD). All results were negative. 3/134 duodenal biopsies showed features suggestive of CD (tTG negative) and 11/134 (8.2%) duodenal biopsies showed lymphocytic duodenosis (LD) (normal villous architecture and increased intraepithelial lymphocytes >25/100 enterocytes) (5/11 tTG sent and negative, 6/11 not done). Conclusion Coeliac disease is a major cause of iron deficiency anaemia in the UK. Tissue transglutaminase antibody is a simple, non-invasive test, which was underused in our cohort. It was performed prior to upper GI endoscopy in only 16.5% of patients. Duodenal biopsies were taken in the majority of cases when indicated in anaemia, though there is room for improvement. While 10.4% had biopsies suggestive of CD, serology to confirm this was only performed in 57.1%. Competing interests None declared. Reference 1. Goddard AF, James MW, McIntyre AS, et al. Guidelines for the management of iron deficiency anaemia (BSG). Gut 2011;60:1309–16.

Celiac Disease With Mild Enteropathy Is Not Mild Disease

Patients with celiac disease have varying degrees of damage to the small intestinal mucosa, ranging from lymphocytic duodenosis with normal villous structure to severe villous atrophy. We assessed whether the severity of mucosal lesions was associated with clinical and laboratory features of celiac disease. We compared demographic, clinical, and laboratory characteristics among patients with celiac disease who were classified based on the severity of duodenal lesions. We analyzed data from 1408 adult patients seen consecutively at a tertiary referral center since 1990. Patients were classified as having villous atrophy (n = 1249) or as having mild enteropathy (n = 159) in the presence or absence of villous atrophy. Similar percentages of patients with villous atrophy, vs mild enteropathy, experienced weight loss (17% vs 17%), gastrointestinal manifestations (70% vs 70%), extraintestinal manifestations (66% vs 57%), and other associated conditions (19% vs 23%). More patients with villous atrophy than patients with mild enteropathy developed osteopenia or osteoporosis (22% vs 5%; P = .0005). Greater percentages of patients with villous atrophy than those with mild enteropathy also had anemia (42% vs 29%; P = .002), folate deficiency (75% vs 64%; P = .02), hypocholesterolemia (7% vs 2%; P = .02), hypocalcemia (26% vs 13%; P = .004), or hyperparathyroidism (45% vs 29%; P = .004). Although osteopenia, osteoporosis, and alterations in laboratory parameters are prevalent among patients with celiac disease with mild enteropathy, they are more prevalent and severe in those with villous atrophy. The prevalence of associated conditions is similar between these groups. These results indicate that celiac disease with mild enteropathy is not mild disease, but requires treatment with a gluten-free diet.

Is a gluten-free diet necessary in Marsh I intestinal lesions in patients with HLADQ2, DQ8 genotype and without gastrointestinal symptoms?

To describe whether a gluten-free diet (GFD) is indicated in Marsh I gluten-sensitive enteropathy where gastrointestinal symptoms are not present. Arguments are provided to prescribe a GFD to manage extraintestinal symptoms. By contrast, there are not enough reasons to prescribe a GFD to prevent long-term complications. Population-based and prospective observational studies have found that lymphocytic duodenosis may be due to not just gluten-sensitive enteropathy but also due to other aetiologic factors. Marsh I type lesions may be the cause of iron-deficiency anaemia of unknown aetiology which is reverted by a GFD. A similar effect seems to occur with bone mineralization and hypertransaminasemia. The beneficial influence of a GFD reducing lymphoma and coeliac disease-related mortality remains controversial. An appropriate differential diagnosis of the lymphocytic duodenosis is essential before a GFD is indicated. As a third of patients remained undiagnosed, in spite of genetic study and specific coeliac serology, flow cytometry and transglutaminase antibodies in duodenal tissue may be helpful in establishing gluten-sensitive enteropathy diagnosis. Future studies should assess whether lymphoma risk is reduced by a GFD in Marsh I patients. Also a more precise benefit in bone mineralization in this setting is needed.

PTU-132 Increased duodenal intra epithelial lymphocytes (IELS) are associated with recurrent abdominal pain and parasite infection but not Helicobacter pylori in a paediatric Chilean cohort

IntroductionFunctional Recurrent Abdominal Pain (RAP) is a paediatric functional gastrointestinal disorder with poorly investigated pathophysiology. Proposed aetiology varies and the diagnosis is characterised by Rome III criteria. Some studies consider...

PWE-183 Investigations for coeliac disease in iron deficiency anaemia—are we following BSG guidelines?

IntroductionBSG guidelines for the investigation of iron deficiency anaemia (2011)1 recommend screening of these patients for coeliac disease (CD) by serology. Small bowel biopsy is recommended at OGD if coeliac...

OC-102 Coeliac disease, anti-inflammatory drugs or Helicobacter pylori are the most common identifiable causes of lymphocytic duodenosis

IntroductionLymphocytic duodenosis (LD) is found in 2% of duodenal biopsies. LD is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. This is more commonly recognised...

Sa1321 Lymphocytic Duodenosis Without Villous Atrophy Within and Outside the Spectrum of Celiac Disease: Differences of Clinical Phenotype

Sa1321 Lymphocytic Duodenosis Without Villous Atrophy Within and Outside the Spectrum of Celiac Disease: Differences of Clinical Phenotype

Sa2003 Increased Duodenal Intra Epithelial Lymphocytes (IELs) are Associated With Recurrent Abdominal Pain and Parasite Infection but Not Helicobacter pylori in a Paediatric Chilean Cohort

Introduction Functional Recurrent Abdominal Pain (RAP) is a paediatric functional gastrointestinal disorder with poorly investigated pathophysiology. Proposed aetiology varies and the diagnosis is characterised by Rome III criteria. Some studies consider Helicobacter pylori to be a cause of RAP, while others disagree. The aim of this study was to investigate upper gastrointestinal pathology in a cohort of 123 children in Chile with respect to RAP, H pylori infection and other concurrent infection. Methods This blinded retrospective and IRB-approved study analysed biopsies taken from the gastric antrum and body and the duodenum in 123 Chilean children referred to endoscopy (with informed parental consent). Histopathology was evaluated against a clinical database which included symptoms, symptom duration and endoscopy findings. Rome III criteria were used to assign RAP to the relevant cases. All patients had stool microbiology and parasitology. H pylori infection was assessed by serology and histology. In the duodenum, routine histopathology and also eosinophil counts (in 5HPF ×40 magnification), were performed by microscopy. IELs/100 enterocytes were counted. Independently those patients with IELs >25 had serology performed for coeliac disease. Results Overall 105 patients were diagnosed with RAP and 12 patients were able to act as controls, having no symptoms of RAP or concurrent infection. The Rome III diagnosis of RAP was significantly associated with higher IEL counts (>20 in 74 patients) compared to controls (p=0.04). Furthermore, a higher IEL count was also positively associated with parasitic infection (nine with parasites) (p=0.02). Of 16 patients with lymphocytic duodenosis, (>25 IELs per 100 enterocytes) only three were infected by H pylori . One had coeliac disease with positive serology. Antral nodularity was observed in association with lymphoid follicles (p≤0.01) and H pylori infection (p H pylori but infection was not significantly associated with RAP (p=0.55) or parasite infection, as concurrent infection was present in only 2 patients (p=0.24). Conclusion From this study, low grade inflammation, manifest by increased IELs, may be associated with RAP and also parasitic infection. H pylori is not associated with parasite infection. However, as eosinophilia was not significantly associated with the condition further investigation is required to elucidate the potential involvement of innate immunity, including mast cells. Furthermore, there is no association between H pylori infection and RAP. Funded by EU CONTENT Project (INCO-CT-2006-032136), CONICYT/BM (RUE #29) and Fondecyt #1100654 (Chile). Competing interests None declared.

Lymphocytic duodenosis: Aetiology and long-term response to specific treatment

BackgroundThe clinical significance of lymphocytic duodenosis remains unclear. AimTo prospectively assess the aetiology of lymphocytic duodenosis and the patterns of clinical presentation. MethodsNinety consecutive patients with lymphocytic duodenosis and clinical symptoms of the coeliac disease spectrum were prospectively included. All subjects underwent serological testing and HLA genotyping for coeliac disease, assessment of Helicobacter pylori infection, and parasite stool examination. Intake of non-steroidal anti-inflammatory drugs was also recorded. The final aetiology of lymphocytic duodenosis was evaluated on the basis of the long-term response to specific therapy. ResultsMore than one initial potential aetiology was observed in 44% of patients. The final diagnosis was gluten-sensitive enteropathy alone or associated with Helicobacter pylori infection in 43.3%, Helicobacter pylori infection (without gluten-sensitive enteropathy) in 24.4%, non-steroidal anti-inflammatory drugs intake in 5.5%, autoimmune disease in 3.3%, and parasitic infection in 2.2%. Among first degree relatives and patients with chronic diarrhoea, the most common final diagnosis was gluten-sensitive enteropathy. In contrast, in the group presenting with chronic dyspepsia the most common diagnosis was Helicobacter pylori infection (‘Diarrhoea’ vs ‘Dyspepsia’ groups, p=0.008). ConclusionsLymphocytic duodenosis is often associated with more than one potential initial aetiology. Clinical presentation may be useful to decide the initial therapeutic approach with these patients.

An update in the diagnosis of coeliac disease

Coeliac disease is increasing in prevalence, which is currently estimated at one in 100 of the population and may occur de novo in adults. The diagnosis requires a joint clinicopathological approach; the recommended first-line test is serology with immunoglobulin A (IgA) tissue transglutaminase and IgA endomysial antibodies. These serological tests show high levels of sensitivity and specificity, but biopsy is the gold standard to confirm the diagnosis. It is important that both tests are performed before the introduction of a gluten-free diet. Although the classical histopathology changes of coeliac disease with partial or total villous atrophy are well recognized, the pathology classification of coeliac disease is changing, with recognition that coeliac disease may show minimal pathology (normal architecture and an intraepithelial lymphocyte count/100 enterocytes ≥ 25). This entity is also described as lymphocytic duodenosis, and recommendation of follow-up serology testing is paramount in this condition. Follow-up of patients with coeliac disease is warranted, as normal serology does not predict mucosal recovery. Failure to heal predicts risk of progression to refractory coeliac disease and malignancies. Refractory coeliac disease occurs in 1-2% of patients and this diagnosis requires a combined clinical and histopathology approach with immunocytochemistry.