Histology of the terminal ileum in coeliac disease

BACKGROUND: The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten-sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy. METHODS: Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs). RESULTS: One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P< 0.005) in the coeliac group than among controls (mean per 100 enterocytes 26 versus 10). An ileal IEL count > or =25 had a sensitivity for duodenal villous atrophy (VA) of 60% and specificity of 100%. CONCLUSIONS: Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.     

Histology of the terminal ileum in coeliac disease

Background: The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten‐sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy. Methods: Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs). Results: One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P?Conclusions: Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.     

Capsule endoscopy: An alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease?

BACKGROUND: Villous atrophy present on a duodenal biopsy remains the 'gold standard' diagnostic test for coeliac disease. However, endoscopic biopsy may cause morbidity and discomfort. Our aim was to evaluate wireless capsule endoscopy as an alternative test for the recognition of villous atrophy. METHOD: Twenty-one patients with a positive endomysial antibody referred for endoscopy and duodenal biopsy were also offered a wireless capsule endoscopy to evaluate their small bowel. Concurrently, other patients (n=23) referred for a wireless capsule endoscopy acted as controls. Wireless capsule endoscopy reports were assessed for the presence of villous atrophy by one blinded investigator. RESULTS: Twenty endomysial antibody positive patients subsequently had villous atrophy on duodenal biopsy. The controls all had normal duodenal biopsies (with a negative endomysial antibody) and no evidence of villous atrophy noted on their wireless capsule endoscopy. Of the 20 endomysial antibody positive patients with confirmed villous atrophy on biopsy, 17 had villous atrophy also detected by wireless capsule endoscopy. The sensitivity, specificity, positive and negative predictive values for wireless capsule endoscopy recognising villous atrophy were 85%, 100%, 100%, 88.9%, respectively. CONCLUSION: Wireless capsule endoscopy may be an option to recognise villous atrophy in patients with a positive endomysial antibody who are unwilling, or unable to have a gastroscopy. However, a negative test should be followed by a biopsy if coeliac disease is to be excluded.     

The occurrence of terminal ileal histological abnormalities in patients with coeliac disease

INTRODUCTION: Coeliac disease causes histological changes throughout the small bowel, but is often a proximal lesion. We wanted to assess whether terminal ileal histological abnormalities occurred more commonly in patients with coeliac disease and if specific assessment of intraepithelial lymphocytes increases the recognition of undiagnosed coeliac disease. METHODS: Terminal ileal biopsies were prospectively examined over a 3-year period (April 2001-May 2004). Patients were included if they were found to have a synchronous duodenal biopsy that gave a new diagnosis of coeliac disease (n=20). Terminal ileal biopsies taken at colonoscopy during the same period were also examined from four groups of patients: coeliac disease established on a gluten-free diet but with persisting symptoms (n=25), inflammatory bowel disease (n=47), chronic diarrhoea (n=44) and polyp surveillance (n=47). All biopsies were graded according to the Marsh criteria and an intraepithelial lymphocytes count per 100 enterocytes was obtained. RESULTS: There was only one patient from all five groups who had villous atrophy of the terminal ileal. This patient had a new diagnosis of coeliac disease. The mean intraepithelial lymphocytes count in the coeliac disease group was 23.7 intraepithelial lymphocytes/100 enterocytes. This was significantly higher than the control groups: coeliac disease on a gluten-free diet=17.5 (p<0.012), inflammatory bowel disease=12.3 (p<0.0001), diarrhoea=12.6 (p<0.0001) and polyp=13.7 (p<0.0002). Validating terminal ileal villous intraepithelial lymphocytes counts as a test for coeliac disease using an intraepithelial lymphocytes/100 enterocytes of >25 gives a sensitivity of 45% and a specificity of 97.8%. CONCLUSION: Routinely quantifying terminal ileal intraepithelial lymphocytes may be of limited clinical value. However, subjective recognition of raised intraepithelial lymphocytes on a terminal ileal biopsy should alert the clinician to the possibility of coeliac disease.     

A microarray screen for novel candidate genes in coeliac disease pathogenesis

BACKGROUND AND AIMS: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. METHODS: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy (Marsh III) and seven control individuals with normal biopsies (Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. RESULTS: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly (p<0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes (p<0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. CONCLUSIONS: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy.     

Continuous Infusion of Cholecystokinin Leads to Down-Regulation of the Cholecystokinin-A Receptor in the Rat Pancreas

Background: Coeliac disease may present with dyspepsia or reflux. There are characteristic duodenal appearances associated with villous atrophy (mosaic pattern mucosa and loss, reduction in number or scalloping of duodenal folds) which may prompt small-bowel biopsy during routine upper gastrointestinal endoscopy. These appearances were sought in patients referred by their general practitioners for open-access endoscopy (OAE), to determine the prevalence and significance of coeliac disease as a cause of symptoms. Methods: Five hundred consecutive patients undergoing OAE by one consultant gastroenterologist were studied. Forceps biopsy specimens from the distal duodenum were taken if appearances were suggestive. If villous atrophy was confirmed, the response of symptoms to dietary gluten exclusion was assessed. Results: Ten patients had suggestive endoscopic appearances, of whom eight had villous atrophy, giving a prevalence of coeliac disease of 1.6% (1:63). All eight had mosaic pattern mucosa, with three also having reduction of duodenal folds, and four having scalloped folds. All had serum endomysial antibodies (EmA). Apart from diarrhoea, described by one patient, there were no symptoms of `typical' coeliac disease at diagnosis: three patients were overweight. After dietary gluten exclusion all reported symptomatic improvement, with disappearance of EmA in five patients to date. Conclusions: There is a high prevalence of coeliac disease among patients undergoing OAE, which is relevant to their clinical symptoms and which can be identified by careful endoscopic inspection of the duodenum.     

Intestinal disaccharidase deficiency without villous atrophy may represent early celiac disease

BACKGROUND: Intestinal disaccharidase activities are decreased in untreated celiac disease and also in other conditions without villous atrophy. Of 908 patients examined for suspected malabsorption, 37 (4.1%) had generalized disaccharidase deficiency without villous atrophy. The aim was to determine if generalized disaccharidase deficiency without villous atrophy represented latent celiac disease. METHODS: Case notes and histology of the 37 patients were reviewed. History and blood investigations including antigliadin and endomysial antibodies were checked. Where celiac disease was suspected, endoscopic duodenal biopsies for histology and disaccharidase estimation were repeated. RESULTS: Of the initial 37 patients, 6 patients had had repeat endoscopic biopsies; one having celiac disease. A further 18 patients were reviewed. The remainder declined further investigation. Eight had repeat endoscopic duodenal biopsies; one had celiac disease. Two with positive celiac serology also had enteroscopy with jejunal biopsies; both had celiac disease. CONCLUSIONS: At least 11% of patients with generalized disaccharidase deficiency without villous atrophy develop celiac disease. Enteroscopic biopsies from distal duodenum and proximal jejunum should be considered as the next investigation if endomysial or antigliadin antibodies are positive.     

Seronegative Celiac Disease: Increased Prevalence with Lesser Degrees of Villous Atrophy

Our aim was to assess differences in the sensitivities of serologic tests used for the diagnosis of celiac disease among patients with varying degrees of villous atrophy. Among 115 adults with biopsy-proven celiac disease who fulfilled strict criteria, including serologic testing at the time of diagnosis and response to a gluten-free diet, 71% had total villous atrophy and 29% partial villous atrophy. Endomysial antibody was positive in 77% of those with total villous atrophy, compared to 33% with partial villous atrophy (P < 0.001). There was no difference in sensitivity when the type of presentation (classical vs. silent) was compared. Endomysial antibody-positive and negative patients did not differ with respect to age at diagnosis, duration of symptoms, mode of presentation, or family history of celiac disease. All anti-tissue transglutaminase-positive patients had TVA on biopsy. Seronegative celiac disease occurs. Endomysial antibody positivity correlates with more severe villous atrophy and not mode of presentation of celiac disease. Serologic tests, in clinical practice, lack the sensitivity reported in the literature.     

Coeliac disease diagnosed by means of duodenoscopy and endoscopic duodenal biopsy

Nineteen patients with suspected coeliac disease were examined by duodenoscopy and biopsy. In all patients a histopathology consistent with coeliac disease was demonstrated in endoscopic biopsies of the duodenal mucosa. On close-up view villous atrophy was seen in vivo. Fourteen patients were re-examined on a gluten-free diet. In 13 patients a restitution of the duodenal mucosa was shown. Duodenoscopy combined with biopsy seems to be a reliable method for the assessment of the mucosal change in coeliac disease.     

Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue

BACKGROUND: Clonal T cell receptor (TCR) gene rearrangements and loss of T cell antigens such as CD8 and TCR-beta in intraepithelial lymphocytes (IELs) may indicate the development of an enteropathy-type intestinal T cell lymphoma (EITCL) in patients with refractory sprue. AIMS: To define the diagnostic value of these markers in duodenal biopsies from patients with villous atrophy as a result of various underlying disorders. PATIENTS AND METHODS: Duodenal biopsies from eight patients with coeliac disease and five patients with villous atrophy caused by defined disorders were compared with three patients with refractory sprue evolving into overt EITCL, two patients with ulcerative jejunitis, and with eight patients with overt EITCL, for expression of CD3, CD4, CD8, and TCR-beta in IELs using immunohistochemistry and for clonal TCR-gamma gene rearrangements using polymerase chain reaction. In addition, biopsies from six consecutive patients with refractory sprue of uncertain cause were examined. RESULTS: Clonal TCR-gamma gene rearrangements were found in all resected tumours of patients with EITCL, in 3/8 duodenal biopsies of patients with EITCL, in 2/2 patients with ulcerative jejunitis, in 2/3 patients with refractory sprue evolving into overt EITCL, and in 1/6 patients with refractory sprue. No rearrangements were found in biopsies from patients with refractory sprue caused by defined disorders or those with coeliac disease. Clonality in duodenal biopsies was associated with an abnormal phenotype of IELs in all cases and in all but one case in patients with evidence of underlying coeliac disease. Specificity for detection of an EITCL using immunohistology was 77% for CD8 and for TCR-beta staining, and 100% for detection of a clonal TCR-gamma gene rearrangement. Sensitivity was 62% for staining with CD8 and clonality investigation, while sensitivity reached 100% for TCR-beta staining in all investigated patients with EITCL. CONCLUSIONS: Clonal proliferations of phenotypically abnormal IELs in refractory sprue represent an early manifestation of EITCL, for which the term "sprue-like intestinal T cell lymphoma" is proposed. This constellation is also found in duodenal biopsies from patients with an overt EITCL and is not related to other sprue syndromes, resulting in a high specificity for detection of an EITCL or refractory sprue evolving into EITCL. Overt EITCL may develop directly from coeliac disease without a precursor lesion (refractory sprue with clonal IELs) being demonstrable in duodenal biopsies or via a "sprue-like intestinal T cell lymphoma". This latter entity is a complication of coeliac disease.     

Duodenal eosinophils as predictors of symptoms in coeliac disease: a comparison of coeliac disease and non-coeliac dyspeptic patients with controls

Abstract

Introduction: Duodenal eosinophilia is a key feature of functional dyspepsia, particularly in those with early satiety. Duodenal eosinophilia is also recognised in coeliac disease, although its relevance to symptoms is not understood. We aimed to determine if duodenal eosinophilia is present in patients with coeliac disease presenting with dyspepsia, and whether other histological characteristics were associated with clinical features on presentation.

Methods: The coeliac study population comprised 61 patients with a new presentation of coeliac disease to a single centre from 2003 to 2013. A standard symptom assessment was documented for all patients. The control population (55 adults) presenting for endoscopy without coeliac disease was drawn from the same centre with similar demographics for age and gender. Duodenal biopsies from both groups were assessed for eosinophil counts and histological features.

Results: Dyspepsia was present in 18.0% of coeliac patients and early satiety in 24.6%. The eosinophil counts were significantly higher in the stomach (12.1/mm² vs. 4.0/mm², p?<?.001) and duodenum (60.4/mm² vs. 18.0/mm², p?<?.001) of coeliac patients compared with controls. There was no significant difference in the mean duodenal eosinophil count in coeliac disease with and without early satiety (55.4/mm² vs. 66.9/mm², p?=?.51). Duodenal eosinophilia was not associated with the severity of coeliac enteropathy. The degree of villous atrophy was associated with iron deficiency at presentation (p?=?.01), but not symptoms.

Conclusions: Although duodenal eosinophil counts are higher in coeliac disease than controls, we were not able to demonstrate an association with presenting symptoms or markers of disease severity.     

Intestinal Disaccharidase Deficiency Without Villous Atrophy May Represent Early Celiac Disease

Background: Intestinal disaccharidase activities are decreased in untreated celiac disease and also in other conditions without villous atrophy. Of 908 patients examined for suspected malabsorption, 37 (4.1%) had generalized disaccharidase deficiency without villous atrophy. The aim was to determine if generalized disaccharidase deficiency without villous atrophy represented latent celiac disease. Methods: Case notes and histology of the 37 patients were reviewed. History and blood investigations including antigliadin and endomysial antibodies were checked. Where celiac disease was suspected, endoscopic duodenal biopsies for histology and disaccharidase estimation were repeated. Results: Of the initial 37 patients, 6 patients had had repeat endoscopic biopsies; one having celiac disease. A further 18 patients were reviewed. The remainder declined further investigation. Eight had repeat endoscopic duodenal biopsies; one had celiac disease. Two with positive celiac serology also had enteroscopy with jejunal biopsies; both had celiac disease. Conclusions: At least 11% of patients with generalized disaccharidase deficiency without villous atrophy develop celiac disease. Enteroscopic biopsies from distal duodenum and proximal jejunum should be considered as the next investigation if endomysial or antigliadin antibodies are positive.     

Coeliac proctitis

An increased association of ulcerative colitis and coeliac disease has been reported, as have the results of several small-bowel biopsy studies in ulcerative colitis. Forty-two patients from a population of 438 patients with coeliac disease had rectal biopsies. Fourteen of these showed inflammation of various degrees of severity, including three compatible with a diagnosis of ulcerative colitis. The presenting complaint in 34 of these patients was diarrhoea or steatorrhoea. Twenty-seven patients had coeliac disease diagnosed at the same time or after their rectal biopsy. The other 15 were previously diagnosed coeliacs. Twelve of the 14 patients with abnormal rectal biopsy specimens were known to have subtotal/total villous atrophy at the time of rectal biopsy. Proctitis as seen in these coeliac patients had no unique features to differentiate it from proctitis caused by other disorders. The diarrhoea/steatorrhoea stopped in all patients on commencement of a gluten-free diet, except in those with ulcerative colitis. Proctitis is common in patients with coeliac disease presenting with diarrhoea/steatorrhoea. This study supports the finding of an increased association of coeliac disease and ulcerative colitis and is, to our knowledge, the first rectal biopsy study of a coeliac population.     

Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy

OBJECTIVES: It is generally believed that in gluten-sensitive enteropathy or celiac disease (CD), mucosal lesions may have a patchy distribution. We wanted to verify this concept and establish whether one or more biopsy samples are needed in order to make a correct diagnosis of CD. METHODS: One hundred and twelve consecutive children with positive antiendomysium (EMA) or antitissue transglutaminase (tTGA) antibodies, referred to us for suspected CD, were enrolled in a prospective fashion. During upper GI endoscopy four to five biopsies were taken from Treitz and/or distal duodenum (D3), intermediate duodenum (D2), proximal duodenum (D1), and duodenal bulb (B). Histologic lesions were classified according to Marsh criteria modified by Oberhuber. RESULTS: A total of 110 patients, all HLA-DQ2 or DQ8 positive, had a final diagnosis of CD (59 classic, 28 atypical, and 23 silent): 102/110 (92.7%) had type 3 lesion-(a) mild, (b) moderate, or (c) severe-in at least one site and 94/110 (85.4%) had villous atrophy (VA) of some degree in all sites. VA of identical degree was present in all biopsy sites in 55/110 (50%) patients. Total VA (type 3c) was present in at least one site in 85/110 (75%), in all sites in 50/110 (45.4%), and significantly increased in aborad direction ((chi(2) > 26.22 with (= 0.01 and d.f. (degrees of freedom) = 12). Eight out of 110 (7.2%) CD patients had exclusively type 1 or 2 lesions, no patient had lesion variability >1 degree and none had normal biopsies. There was no correlation between type or distribution of histologic lesions and clinical presentation of CD. CONCLUSIONS: Mucosal atrophy is present in 85% of patients with CD and total VA is significantly more frequent in distal duodenum or proximal jejunum. Fifty percent of patients have identical VA throughout the duodenum and no duodenal areas are histologically normal. In genetically susceptible children with positive serology, a diagnosis of CD can reliably be made even if biopsies are not taken from the distal duodenum or jejunum.     

Regression of lactose malabsorption in coeliac patients after receiving a gluten-free diet

OBJECTIVE: In a recent study by our group, it was shown that a large proportion of patients with lactose malabsorption and with no bacterial overgrowth are affected by silent coeliac disease (CD). Our aim was to evaluate the effect of a gluten-free diet on lactose malabsorption assessed using the hydrogen lactose breath test (LBT) and also the relationship with normalization of duodenal biopsies in coeliac patients. MATERIAL AND METHODS: Fifteen patients (11 F, 4 M; mean age 35.8+/-6) affected by CD with a positive LBT and negative glucose breath test were enrolled. All were started on a gluten-free diet and were re-evaluated after 6 months by LBT and after 12 months by both LBT and upper gastrointestinal endoscopy with biopsies. RESULTS: LBT normalization was observed in 1 out of 15 patients (6.7%) after 6 months and in 9 of the remaining 14 (64.2%) after 12 months. Duodenal biopsies showed normal villi in 8 patients, partial villous atrophy in 5 and total atrophy in 2. CONCLUSIONS: The present study shows that a large proportion of CD patients experience a regression of lactose malabsorption after receiving a gluten-free diet. This may be related to normalization of the brush border with an improvement of lactase enzyme activity. LBT should be performed after 12 months in CD patients on a gluten-free diet in order to assess the persistence/disappearance of lactose malabsorption, thus avoiding an unnecessary lactose-free diet.     

The value of duodenal biopsy within routine upper endoscopy: a prospective study in 1000 patients

BACKGROUND AND AIM: Several gastrointestinal diseases are localised in the small bowel and are confirmed by duodenal biopsies upon upper gastrointestinal endoscopy. However, the clinical value of routine duodenal biopsies during endoscopy has not been satisfactorily defined and was assessed in the current study. METHODS: In 1000 consecutive patients duodenal biopsies were performed during routine upper gastrointestinal endoscopy. Endoscopic diagnoses, symptoms and the prevalence of anaemia were correlated with the histological diagnoses. RESULTS: Coeliac disease and giardiasis was diagnosed in 18 and two patients, respectively (2.0 % of all cases). In 11 (55 %) patients the diagnosis was already made macroscopically during endoscopy. The sensitivity for endoscopic diagnosis of coeliac disease MARSH III was 84.6 %. There was no correlation between clinical symptoms, the prevalence of anaemia and the diagnosis of coeliac disease or giardiasis in our cohort. CONCLUSION: Endoscopic diagnosis of advanced celiac disease (MARSH III) can be made with high sensitivity and specifity. Nevertheless, duodenal biopsy is necessary for the diagnosis of early coeliac disease or giardiasis. However, the routine duodenal sampling of normal mucosa during gastrointestinal endoscopy cannot be recommended.     

Reliance on Serum Endomysial Antibody Testing Underestimates the True Prevalence of Coeliac Disease by One Fifth

Background: Although IgA endomysial antibody (EmA) is currently the serologic test of choice in selecting suspected coeliac patients for duodenal biopsies, false-negative cases have been reported and may be more common than previous studies suggest. We assessed the sensitivity of EmA for patients with biopsy-confirmed villous atrophy (VA). Methods: We studied 89 patients without IgA deficiency for whom biopsy had not been primarily prompted by a positive EmA result. VA was graded as partial, subtotal, or total (PVA, STVA, TVA). Serum EmA was assayed with indirect immunofluorescence. Results: The sensitivity of EmA for VA was 78% (69 of 89) and was similar for PVA (79%) and ST/TVA (77%). Only 4 of the 20 EmA-negative patients had increased serum IgA-class antigliadin antibody levels as measured with enzyme-linked immunosorbent assay. All seronegative patients who complied with dietary gluten exclusion responded clinically, with histologic improvement after 12 months in 8 (67%) of 12 patients who had follow-up biopsies. Conclusions: EmA-negative coeliac disease is common. Reliance on EmA testing to select patients for biopsy will result in significant underdiagnosis.     

Duodenal Disaccharidase Activities in the Follow-up of Villous Atrophy in Coeliac Disease

Background: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. Methods: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade 1 = slight villous atrophy, that is, cryptic component 30%- 50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component &gt;90%. The enzyme activities of the disaccharidases were determined as U/g protein. Results: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity &lt;150 U/g protein), 86% for sucrase (&lt;40 U/g protein) and 71% for lactase (&lt;20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. Conclusions: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.     

The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.

BACKGROUND/OBJECTIVE: Circulating antibodies offer a noninvasive diagnostic screening test in patients with coeliac disease with severe histopathological abnormalities. This study assesses for the first time the sensitivity and reliability of anti-endomysium in screening for coeliac disease in patients with milder forms of villous atrophy using human umbilical cord and monkey ileum. MATERIALS AND METHODS: Serum from 124 adults and children > 2 years old including 33 patients with coeliac disease on a gluten-free diet and 91 patients referred to the laboratory for screening was studied. The presence of IgA-anti-gliadin (AGA) (ELISA) and IgA-anti-endomysium (EMA) was detected in the serum using monkey ileum and human umbilical cord (HUC) substrates. Patients with abnormal serology results or severe clinical complaints were invited to attend for a small-bowel biopsy. The prevalence of EMA detected on monkey ileum and HUC was compared with the histopathological features of coeliac disease at presentation. Fifty-three of the 91 patients screened for coeliac disease underwent a small intestinal biopsy. RESULTS: Twenty-three of the 91 patients suspected of having coeliac disease had coeliac disease. The EMA test was positive in 18 of 23 using both monkey ileum and HUC (sensitivity 78%). Partial villous atrophy (PVA) was seen in four of the five EMA-negative patients, and subtotal/total villous atrophy (SVA/TVA) was demonstrated in 18 of the 23 cases with positive EMA. Both substrates detected identical positive cases. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on monkey ileum. One patient was EMA-negative on monkey ileum but positive on HUC and one patient who was EMA-positive on monkey ileum was EMA-negative on HUC. Only one of 33 coeliac disease patients on gluten-free diet for more than one year with persisting TVA had positive EMA. The rest of the cases had a negative EMA on both HUC and monkey ileum. CONCLUSION: A negative result for EMA in coeliac disease patients with a normal IgA value does not exclude the diagnosis of coeliac disease. A positive EMA is seen mostly in those coeliac disease patients with severe tissue damage (SVA/TVA). EMA has a low sensitivity in coeliac disease patients with PVA in spite of use of different substrates.     

Duodenal disaccharidase activities in the follow-up of villous atrophy in coeliac disease

BACKGROUND: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. METHODS: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade I = slight villous atrophy, that is, cryptic component 30%-50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme activities of the disaccharidases were determined as U/g protein. RESULTS: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. CONCLUSIONS: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.