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.     

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.     

Intraepithelial lymphocyte mitosis in a jejunal biopsy correlates with intraepithelial lymphocyte count, irrespective of diagnosis.

When there is villus atrophy in a jejunal biopsy, intraepithelial lymphocyte (IEL) mitosis correlates with a diagnosis of coeliac disease. We have examined the significance of IEL mitosis in jejunal biopsies with normal villi. Counts of IEL per 100 villus enterocytes, and IEL mitosis per 1000 IEL, were carried out in 81 jejunal biopsies. Thirty one were from patients with coeliac disease or dermatitis herpetiformis, and many of these, from treated patients, were histologically normal; 40 were from patients with other diagnoses, selected to include biopsies with a high IEL count (greater than 40 IEL per 100 enterocytes) but normal villi. Three coeliacs and 10 dermatitis herpetiformis patients had an IEL count of less than 40, and no IEL mitoses were found in these biopsies. Two dermatitis herpetiformis patients had IEL counts of 43.7% and 43.9%, with no IEL mitoses, but in all other coeliac and dermatitis herpetiformis biopsies high IEL counts were associated with IEL mitotic indices between 0.05% and 1.77%. In the non-coeliac, non-dermatitis herpetiformis group, no IEL mitoses were found in the 22 biopsies with IEL count less than 43%. In the others, IEL counts ranged from 44.8% to 127.0%, and IEL mitoses were present, with mitotic indices ranging from 0.06% to 0.49%. This work shows that IEL mitosis in a jejunal biopsy is not specific for coeliac disease, but occurs whenever there is an increased density of IEL within the villus epithelium.     

Isolated ileal villous atrophy: a rare cause of chronic diarrhea. Report of a case and review of the literature

Villous atrophy of the terminal ileum is usually secondary to celiac disease or other diseases. Very few cases of primary ileal villous atrophy have been reported in the literature. We report here the case of a 37-year-old man with chronic diarrhea since childhood without features of malabsorption. The macroscopic and microscopic appearance of the duodenal, ileal and colonic mucosae at endoscopy and contrast radiography of the small bowel was normal. Ileal lesions consisted of total villous atrophy. Search for antinuclear antibodies, anti-endomysium and anti-gliadin IgA and IgG and HIV serology were negative. Serum immunoglobulin level was normal. Diarrhea resolved under treatment with colestyramine.     

Parallel expression of macrophage metalloelastase (MMP-12) in duodenal and skin lesions of patients with dermatitis herpetiformis

BACKGROUND: Dermatitis herpetiformis (DH) is a specific dermatological manifestation of coeliac disease and 80% of DH patients have gluten sensitive enteropathy manifested by crypt hyperplasia and villous atrophy. Matrix degradation mediated by collagenase 1 (MMP-1) and stromelysin 1 (MMP-3) has previously been implicated in the pathobiology of coeliac intestine and cutaneous DH blisters. AIMS: To study expression of stromelysin 2, metalloelastase, collagenase 3, and matrilysin in the intestine and skin of DH patients. METHODS: In situ hybridisation using 35S labelled cRNA probes was performed on duodenal biopsies of 15 DH patients, three samples each of control duodenal or jejunal mucosa, fetal ileal explants, lesional DH skin, and 19 serial biopsies of experimental DH blisters. Immunostaining was used to examine type IV collagen, macrophages (CD68), and 92 kDa gelatinase (MMP-9) in the specimens. RESULTS: Metalloelastase (MMP-12) was abundantly expressed by subepithelial macrophages in both coeliac intestine and spontaneous and induced DH rash. It was also upregulated in the experimental model of coeliac disease (staphylococcal endotoxin B stimulated fetal explants). The only other MMP detected was MMP-9 which did not colocalise with MMP-12. CONCLUSIONS: Upregulation of metalloelastase is associated with T cell mediated immune responses both in the intestine and skin. In addition to modulating macrophage migration, it may contribute to degradation of proteoglycans or basement membrane components in the subepithelial mucosa.     

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.     

Diagnostic methods beyond conventional histology in coeliac disease diagnosis

BackgroundCoeliac disease diagnostic criteria currently require the detection of small bowel mucosal villous atrophy and crypt hyperplasia.AimsTo compare conventional histological examination to the determination of small bowel mucosal intraepithelial lymphocytes (IELs) and to serum and intestinal coeliac autoantibodies in untreated coeliac disease with villous atrophy and in mild enteropathy coeliac disease.Patients and methodsStudy comprised consecutive adult patients with coeliac disease suspicion; villous height–crypt depth ratio (Vh/CrD), the densities of CD3+, γδ+ and villous tip IELs and serum and intestinal transglutaminase 2 (TG2)-targeted autoantibodies were studied. Coeliac disease was diagnosed in 223 and excluded in 608 patients. Further, 66 patients were considered to suffer from mild enteropathy coeliac disease. Control group consisted of 138 patients.ResultsVh/CrD determination detected 77% of untreated coeliac disease patients. Serum coeliac autoantibodies had 84% sensitivity for untreated coeliac disease with villous atrophy and 70% sensitivity for mild enteropathy coeliac disease; the specificity was 100%. Intestinal TG2-targeted autoantibodies had sensitivities of 100% and 93%, and 100% specificity, respectively. γδ+ and villous tip IELs proved more reliable than CD3+ IELs.ConclusionsConventional histological examination as the golden standard in coeliac disease diagnosis is questionable. Serum and especially intestinal TG2-targeted autoantibodies seem promising in future coeliac disease diagnostics.     

Small-bowel barium follow-through is rarely required in patients with a normal ileoscopy and terminal ileal biopsy and a normal or unremarkable colonoscopy

BACKGROUND: There is an increase of reliance on ileoscopy in preference to small-bowel barium follow-through in the diagnosis of terminal ileal Crohn disease. In this study the role of small-bowel barium follow-through after a normal or unremarkable ileocolonoscopy was investigated. METHODS: A retrospective analysis of all patients who had a colonoscopy followed by a small-bowel barium follow-through over a 7-year period was performed. Patients with a previously established diagnosis of inflammatory bowel disease and those who had colonoscopic evidence of inflammatory bowel disease were excluded. RESULTS: Of the 96 patients who had a normal ileoscopy and normal or unremarkable colonoscopy, 3 had abnormalities detected at small-bowel barium follow-through. Two patients had abnormal terminal ileal biopsies, although the terminal ileum appeared macroscopically normal. The small-bowel barium follow-through helped to establish the diagnosis of Crohn disease. The other patient presented changes consistent with a previously established diagnosis. Of the 47 patients who had a normal or unremarkable total colonoscopy without ileoscopy, I had abnormalities detected at small-bowel barium follow-through consistent with a previously established diagnosis. CONCLUSIONS: Small-bowel barium follow-through is rarely required in patients who have had a normal ileoscopy and terminal ileum biopsy and a normal or unremarkable colonoscopy. It should only be performed if there is a very high index of suspicion of small-bowel pathology. In patients with suspected Crohn disease, it is important to take terminal ileum biopsies even if the ileum appears macroscopically normal at ileoscopy.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in 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.     

Small-bowel barium follow-through is rarely required in patients with a normal ileoscopy and terminal ileal biopsy and a normal or unremarkable colonoscopy

Background: There is an increase of reliance on ileoscopy in preference to small-bowel barium follow-through in the diagnosis of terminal ileal Crohn disease. In this study the role of small-bowel barium follow-through after a normal or unremarkable ileocolonoscopy was investigated. Methods: A retrospective analysis of all patients who had a colonoscopy followed by a small-bowel barium follow-through over a 7-year period was performed. Patients with a previously established diagnosis of inflammatory bowel disease and those who had colonoscopic evidence of inflammatory bowel disease were excluded. Results: Of the 96 patients who had a normal ileoscopy and normal or unremarkable colonoscopy, 3 had abnormalities detected at small-bowel barium follow-through. Two patients had abnormal terminal ileal biopsies, although the terminal ileum appeared macroscopically normal. The small-bowel barium follow-through helped to establish the diagnosis of Crohn disease. The other patient presented changes consistent with a previously established diagnosis. Of the 47 patients who had a normal or unremarkable total colonoscopy without ileoscopy, 1 had abnormalities detected at small-bowel barium follow-through consistent with a previously established diagnosis. Conclusions: Small-bowel barium follow-through is rarely required in patients who have had a normal ileoscopy and terminal ileum biopsy and a normal or unremarkable colonoscopy. It should only be performed if there is a very high index of suspicion of small-bowel pathology. In patients with suspected Crohn disease, it is important to take terminal ileum biopsies even if the ileum appears macroscopically normal at ileoscopy.     

Gliadin induced changes in the expression of MHC-class II antigens by human small intestinal epithelium. Organ culture studies with coeliac disease mucosa.

Jejunal biopsies from 16 treated coeliac disease patients and from nine controls were cultured with and without a peptic-tryptic digest of gliadin. Cultures with a peptic-tryptic digest of maize prolamins were also undertaken. Frozen sections of baseline and cultured mucosa were stained by immunofluorescence with an anti-HLA-DR monoclonal antibody. Before culture the villous epithelium from both controls and treated coeliac disease expressed DR molecules while the crypt epithelium did not. When biopsies from treated coeliac disease were cultured with gliadin the expression of DR was enhanced in the crypt epithelium in eight of 14 cultures and in 11 of 14 was reduced or absent on the villous epithelium. No change was observed in control cultures. We conclude that gliadin is capable of inducing HLA-DR on the crypt epithelium of in vitro cultured coeliac disease mucosa, providing indirect evidence that gliadin may activate cell mediated immune mechanisms within the small bowel mucosa. This model could prove useful in identifying the immunogenic sequence(s) of gliadins and related prolamins.     

Combined terminal ileoscopy and biopsy is superior to small bowel follow-through in detecting terminal ileal pathology

BACKGROUND: Several studies have compared small bowel barium examination with ileoscopy in assessment of terminal ileal disease. Some suggest that ileoscopy is superior in detection of terminal ileal disease whereas others suggest similar disease detection rates for both techniques. AIMS: The aim of this retrospective study was to determine if small bowel follow-through and ileoscopy with terminal ileum biopsy compare favourably at detecting pathology in the terminal ileum. PATIENTS AND METHODS: All colonoscopies with terminal ileoscopy performed over a 16-month period were reviewed. We determined which of these patients had also had small bowel follow-through studies within 2 weeks of colonoscopy. We compared the diagnoses of terminal ileum pathology using ileoscopy with terminal ileal biopsy versus small bowel follow-through. RESULTS: Forty-six patients had both terminal ileoscopy with biopsy and small bowel follow-through. In 19 patients, the terminal ileum was abnormal at ileoscopy and/or biopsy but normal at small bowel follow-through. In 27 patients, terminal ileum findings at small bowel follow-through and at ileoscopy and/or biopsy were compatible. CONCLUSIONS: This study suggests that examination of the terminal ileum by combined ileoscopy and biopsy may be superior to small bowel follow-through at detecting terminal ileal pathology. In our series, many patients received effective treatment that otherwise would not have been offered based on the small bowel follow-through results alone. Using combined ileoscopy and biopsy, microscopic inflammatory changes, otherwise missed without biopsy, can be detected. Retrograde ileoscopy is recommended in patients with a clinical history of organic diarrhoea and/or abdominal pain even in the presence of a normal small bowel follow-through.     

Quantitative histological study of enteropathy associated with HIV infection.

A quantitative histological study was performed on small intestinal biopsies from eight ambulatory patients with HIV infection (AIDS/AIDS-related complex, ARC) and compared with those from 16 normal subjects. Enteropathy was assessed by measurement of villus area, crypt length and mitotic count, as well as duodenal counts of intraepithelial lymphocytes, mucosal mast cells and goblet cells. Enteropathy in subjects with AIDS/ARC was shown by reduced mean villus area of 0.363 (SD 0.081) compared with 0.500 (SD 0.064) mm2 in control subjects (p less than 0.0001), while intestinal crypts were of similar length with 239 (SD 36) compared with 225 (SD 28 microns, but mitotic count was increased to 3.8 (SD 1.2) compared with 2.4 (SD 0.8) (p = 0.01) in the same control subjects. These results indicate villous atrophy with impaired crypt hyperplasia. Duodenal cell counts showed similar numbers of mucosal mast cells, intraepithelial lymphocytes and goblet cells in AIDS/ARC patients and fifteen control subjects.     

Acute gluten challenge in treated adult coeliac disease: a morphometric and enzymatic study.

Using a Quinton hydraulic biopsy tube, jejunal biopsies were obtained from 10 patients with adult coeliac disease in remission and four healthy volunteers before and after administration of gluten fraction III into the proximal duodenum. The biopsies taken at hourly intervals for four hours, were analysed for changes in brush border enzymes, light microscopic appearances, and villous and crypt population counts. The results indicate that mucosal damage occurs within three to four hours of gluten administration with significant falls in brush border enzyme concentrations and villous population counts. The absence of any change in control biopsies indicates that gluten sensitivity is specific to the mucosa of patients with coeliac disease, the timing of the changes being consistent with a type III immune response or direct toxicity. Some recovery of the brush border enzymes but not the villous population was evident 24 hours after gluten administration while the crypt population showed evidence of a compensatory hyperplastic reaction.     

Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet.

Numbers of T cell receptor (TcR) gamma delta+ and alpha beta+ intestinal lymphocytes were studied in 34 coeliac patients in respect of their diet and the grade of villous atrophy. Particular attention was given to a group of 21 patients with coeliac disease according to ESPGAN criteria who were on a well tolerated long term normal diet and in nine of whom the mucosa had returned to normal or nearly normal. A significant increase in TcR gamma delta+ cells was observed in the gut epithelium of coeliac patients compared with age matched controls, and this did not correlate with either the presence of gluten in the diet or with the grade of villous atrophy. Thus, numbers of TcR gamma delta+ intraepithelial lymphocytes (IEL) were considerably above the normal range in four of seven patients on a gluten free diet and in four of nine patients who had recovered a normal or nearly normal mucosa in spite of a normal diet. In contrast, numbers of intestinal TcR alpha beta+ cells varied with the stage of the disease. Their number was high in the epithelium of patients with active coeliac disease (n = 18) but significantly less in patients whose mucosa had returned to normal or nearly normal either after gluten free diet (n = 7) or in spite of a normal diet (n = 9). Immunohistochemical markers of intestinal mononuclear cell activation detected in active coeliac disease were either weakly expressed or absent in the latter patients. It is suggested that TcR alpha beta+ but not TcR gamma delta+ IEL are sensitised to gliadin in coeliac disease, and that only the former cells play a direct part in the pathogenesis of the villous atrophy. The normal counts of TcR alpha beta+ IEL and the absence of detectable mononuclear activation in the biopsy specimens of a few patients who have recovered clinical and histological tolerance to gluten sustains this hypothesis and also suggests that immunological tolerance to gluten may be acquired in a subgroup of coeliac patients. Hte appreciable increase in TcR gamma delta+ IEL observed in some of the latter patients, however, is similar to that observed in latent coeliac disease urging for their careful and prolonged follow up until the role of TcR gamma delta+ IEL in the pathogenesis of coeliac disease is elucidated.     

Making the diagnosis of coeliac disease: is there a role for push enteroscopy?

Coeliac disease is one of the most common genetically based diseases. The wide clinical spectrum of the disease and the availability of highly specific antibody testing have led to an increased number of patients undergoing gastroscopy with distal duodenal biopsies. Histological confirmation of the characteristic small bowel changes with partial or total villous atrophy remain the gold standard for making a diagnosis. Patients with positive antibodies but initially negative or uncertain biopsies pose a particular diagnostic dilemma. Due to the patchiness of the histological changes, push enteroscopy with jejunal biopsies can play a valuable role in this group of patients. Similarly, patients with refractory coeliac disease can benefit from push enteroscopy with jejunal biopsies.     

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.     

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.     

Persistent Mucosal Abnormalities in Coeliac Disease Are Not Related to the Ingestion of Trace Amounts of Gluten

Background: It is expected that in patients with coeliac disease the small-bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in `gluten-free' foods, as defined by the WHO/FAO Codex Alimentarius. Methods: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet. Results: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet; 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS). Conclusion: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.