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.     

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 >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.     

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.     

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.     

Optical coherence tomography in pediatric patients: A feasible technique for diagnosing celiac disease in children with villous atrophy

Background and aimCeliac disease is a common condition with many atypical manifestations, where histology serves as the “gold standard” for diagnosis. A useful new technique, optical coherence tomography, can depict villous morphology in detail, using light waves. This study examined the correlation between the sensitivity and specificity of optical coherence tomography in pediatric patients undergoing esophago-gastro-duodenoscopy for the diagnosis of celiac disease.Materials and methodsA total of 134 children were prospectively enrolled, 67 with a serological suspicion of celiac disease (group 1) and 67 with negative histology for celiac disease (group 2). During a diagnostic esophago-gastro-duodenoscopy we acquired multiple images and films in the four quadrants of the second part of the duodenum, and biopsies were taken in the area where optical coherence tomography had been done. Three patterns of villous morphology were considered: pattern 1 = no atrophy (types 0, 1 or 2 of the Marsh classification); pattern 2 = mild atrophy (type 3a or 3b); pattern 3 = marked atrophy (type 3c).ResultsThe diagnosis of celiac disease was histologically confirmed in all 67 children with positive antiendomysium and/or antitransglutaminase antibodies. Optical coherence tomography correlated with pattern 1 histology in 11/11 cases, pattern 2 in 30/32 (93.8%) and pattern 3 in 22/24 (91.6%). Sensitivity and specificity were 82% and 100%. In the control group there was 100% concordance between optical coherence tomography and histology. The overall concordance between optical coherence tomography and histology in determining patchy lesions was 75%.ConclusionOptical coherence tomography could be a helpful diagnostic tool in children with mild or marked villous atrophy for diagnosing celiac disease during upper gastrointestinal (GI) endoscopy, avoiding biopsies. However, duodenal biopsies are mandatory if the optical coherence tomography shows normal villous morphology in patients with positive antibodies.     

High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease

BackgroundDuodenal biopsy may be unnecessary to confirm celiac disease in patients with high tissue-transglutaminase antibody level.AimsTo define a cut-off value of tissue-transglutaminase antibody with high positive likelihood ratio for duodenal atrophy in patients with suspected celiac disease.MethodsWe retrospectively identified 945 patients with suspected celiac disease and classified according to the method used for tissue-transglutaminase antibody assay: Group A (n = 393, Eu-tTG^® Eurospital), Group B (n = 263; Eu-tTG^® Eurospital) and Group C (n = 289; Celikey^® Phadia). Duodenal histology was graded according to Marsh. Sensitivity, specificity, and positive likelihood ratio were used to evaluate cut-off points of tissue-transglutaminase antibody as predictor of villous atrophy.Results100% specificity and ∞ positive likelihood ratio for duodenal atrophy was observed at a cut-off value of tissue-transglutaminase antibody 5 times higher than the upper limit of normal. CD diagnosis was confirmed by concordance with antiendomysial antibodies, and by reduction of t-TG titre in all patients and improvement of duodenal histology in 80% during gluten-free diet.ConclusionsTissue-transglutaminase antibody level 5-folds the upper limit of normal is 100% specific for duodenal atrophy and using this cut-off biopsy could by avoided in 1/3 of patients. Diagnostic criteria of celiac disease in adults need revision.     

Erosions in the second part of the duodenum in patients with villous atrophy

BACKGROUND: There are various, well-documented, duodenal endoscopic markers caused by the villous atrophy of celiac disease. Another abnormality seen in association with villous atrophy, erosions in the second part of the duodenum, is described. To our knowledge, this finding has not been heretofore described in patients with celiac disease. METHODS: Five patients with celiac disease and erosions were encountered over a period of 2 years. OBSERVATIONS: The erosions were multiple, superficial, and present in the second part of the duodenum but not the duodenal bulb. All 5 patients had findings typical of celiac disease (iron deficiency, osteopenia/osteoporosis), and 4 had at least one other endoscopic marker: scalloped duodenal folds (3), fold loss (2), or mosaic pattern mucosa (2). These patients represented 7% of new cases of celiac disease during the same time period. This pattern of erosion was not observed in over 1200 other patients undergoing upper endoscopy during the study period. CONCLUSIONS: In a European population, the finding of erosions confined to the second part of the duodenum is specific for villous atrophy, although sensitivity is low. Erosions in the second part of the duodenum should be added to the list of endoscopic markers of celiac disease.     

A Retrospective Assessment of the Clinical Value of Jejunal Disaccharidase Analysis

Duncan A, Park RPR, Lee FD, Russell RI. A retrospective assessment of the clinical value of jejunal disaccharidase analysis. Scand J Gastroenterol 1994;29:1111-1116.

Background: The measurement of jejunal disaccharidases is used by several gastroenterologists when investigating suspected small-bowel disease. The clinical value of this analysis is assessed.

Method: The histology and disaccharidase results in 1585 jejunal biopsy specimens were reviewed retrospectively.

Results: Disaccharidase and histology results concurred in most cases (72%). However, disaccharidases were an insensitive indicator of small-bowel disease: low levels were found in only 65% of coeliac patients with villous atrophy, 15% of patients with giardiasis, and 6% of patients with villous atrophy associated with non-coeliac histology. Low disaccharidase levels were sometimes found in patients with normal histology (1.6%) and when biopsy specimens were unwittingly taken from non-jejunal sites (1.4%). Isolated low lactase activities were found in 3.2%. Usually this finding was not clinically relevant because patients had no symptoms of lactose intolerance (38%), had another diagnosis that responded to appropriate treatment (8%), or had no response to a low-lactose diet (14%). In 16 patients sucrase activities were markedly low, and this investigation proved central to the diagnosis of sucrase-α-dextrinase deficiency, which was subsequently confirmed in 9.

Conclusion: Jejunal disaccharidases are clinically useful only in the diagnosis of sucrase-α–dextrinase deficiency. We recommend that their measurement be reserved for the investigation of patients suspected of having this condition.     

All that scallops is not celiac disease

BACKGROUND: Scalloping of duodenal folds as well as a mosaic mucosal pattern, decreased folds, and increased vascularity are markers of duodenal mucosal injury, the most common cause being celiac disease. We have recognized scalloping in patients with a variety of conditions other than celiac disease. METHODS: Clinical, endoscopic and histologic data were reviewed from selected patients with endoscopically visualized scalloped folds along with testing for endomysial antibodies. Biopsy specimens were examined histologically for villous:crypt ratio, intraepithelial lymphocytes, and inflammation. RESULTS: Thirteen patients with scalloped folds underwent endoscopy for the following reasons: family history of celiac disease and osteoporosis, gastrointestinal bleeding, dyspepsia (2), B(12)/ folate deficiency (4), and diarrhea (8). Histologic examination was abnormal in all but 1 patient. Villous atrophy or flattening as evidenced by reduced villous:crypt ratio was seen in 11 of 13 patients. Other abnormalities were edematous or broadened villi (10), intraepithelial lymphocytosis (7), and infiltration of lamina propria (6). An infectious organism was identified in 6 patients (46%). Celiac disease was excluded by the lack of specific biopsy findings combined with endomysial antibody testing. Final diagnoses were normal (1), eosinophilic enteritis (1), giardiasis (1), tropical sprue (4), human immunodeficiency virus-related diseases (6) including human immunodeficiency virus enteropathy (1). CONCLUSION: We conclude that scalloping is not specific for celiac disease but rather a predictor of mucosal disease as evidenced by villous atrophy, widening, and edema.     

Role of the "immersion technique" in diagnosing celiac disease with villous atrophy limited to the duodenal bulb

GOALS: To investigate if the so-called immersion technique during upper endoscopy may be helpful to predict patterns of villous atrophy restricted to the duodenal bulb. BACKGROUND: Patients with celiac disease may have a patchy distribution of duodenal villous atrophy. In some cases, mucosa of duodenal bulb may be the only intestinal area involved. The immersion technique is a novel procedure that allows visualizing duodenal villi directly during endoscopy. STUDY: With this prospective study, the immersion duodenoscopy was performed in 67 celiac subjects to investigate their duodenal villous pattern. Villi were evaluated both in the first and in the second duodenal segment and judged as present or absent (flat mucosa). Results were compared with histology as reference. RESULTS: Among celiac subjects, 49 were newly diagnosed and 18 previously diagnosed celiac patients. Four (8%) newly diagnosed and 7 (39%) previously diagnosed celiac subjects had an extension of the villous atrophy (flat mucosa) limited to the duodenal bulb. The sensitivity, specificity, and positive and negative predictive values of the immersion-based duodenal investigation in predicting areas of duodenal villous atrophy was always 100%. CONCLUSIONS: Immersion technique may be useful for directing duodenal biopsies in celiac subjects with a patchy distribution of villous atrophy. This procedure can avoid blinded sampling of the duodenal mucosa and enhance the diagnostic yield.     

Pilot study on the correlation of optical coherence tomography with histology in celiac disease and normal subjects

BACKGROUND AND AIM: Celiac disease (CD) is a common condition but often it goes unrecognized because characteristic histopathological abnormalities must be found to confirm the diagnosis. A way is needed to select patients who need biopsy of the duodenal mucosa to detect CD. No data are currently available on the use of in vivo optical coherence tomography (OCT), during real-time endoscopic imaging, in the small intestine and, particularly, in the diagnosis of CD. The aim of the present study was to test the utility of OCT in patients undergoing esophagogastroduodenoscopy (EGD) for histological diagnosis. METHODS: Eighteen patients with suspected CD (positive for antigliadin, antiendomysial and antitransglutaminase antibodies) and 22 dyspeptic subjects (negative for these antibodies) who were also examined by EGD, were prospectively enrolled. OCT scans of descending duodenum were taken during diagnostic EGD, with biopsies of the same duodenal area. OCT images and histological specimens were evaluated blindly, analysis being done independently by a gastroenterologist and a pathologist. Three patterns of intestinal villous morphology were considered (1, no atrophy; 2, mild atrophy; 3, marked atrophy). RESULTS: Concordance was total between OCT and histology for villi morphology in both patients and normal subjects. CONCLUSIONS: OCT appears to be a promising method for correctly identifying villous atrophy; it may help in selecting patients for intestinal biopsies, considering the limited usefulness of endoscopic criteria, and may also help the endoscopist to perform target biopsies in mucosal areas where the villi are damaged or absent, considering that CD often causes patchy mucosal lesions.     

Gluten Sensitivity in Patients With Primary Biliary Cirrhosis

Objective : Whereas celiac disease and primary biliary cirrhosis have been reported to coexist in the same patient, the frequency of this relationship has not been clarified. Nowadays, the concept of celiac disease has been extended from that of a severe enteropathy to a broader concept of gluten-driven intestinal immunological response. In this study we assessed features of gluten sensitivity in a cohort of patients with primary biliary cirrhosis. Methods : Ten patients with primary biliary cirrhosis were evaluated a mean of 2 yr after diagnosis. The following features of gluten sensitivity were assessed: serum antigliadin and endomysial antibodies, small bowel histology (degree of atrophy and quantitative histological parameters), the presence of the typical celiac HLA genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa after local gluten instillation (rectal gluten challenge). Results : Overall, three patients presented evidence of gluten sensitivity. AH three had abnormal liters of antigliadin antibody type IgA and one was positive for endomysial antibody. Two patients had partial villous atrophy. The rectal gluten challenge showed a celiac-like response, evidenced by an increase in intraepithelial lymphocyte infiltration after gluten exposure, in the three patients. The characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in three patients. One of them also exhibited other features of gluten sensitivity. However, despite evidence of gluten intolerance, patients had minimal or no symptoms characteristic of celiac disease. Conclusion : We detected features of gluten sensitivity in a high proportion of patients with primary biliary cirrhosis. Further studies should be performed to elucidate the clinical significance of this association.     

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.     

HLA-DQ typing in the diagnosis of celiac disease

OBJECTIVE: More than 95% of celiac patients share the major histocompatibility complex II class human leukocyte antigen (HLA) DQ2 or DQ8 haplotype; patients negative for both types are unlikely to suffer from celiac disease. Our aim was to investigate whether HLA-DQ2 and -DQ8 typing is helpful when diagnosis is uncertain because of the absence of unequivocal small bowel villous atrophy. METHODS: HLA-DQ2 and -DQ8 typing was carried out in 59 patients evincing nondiagnostic small bowel mucosal lesion or positive celiac serology, and in 17 patients maintaining a gluten-free diet without biopsy-proven celiac disease. HLA findings were compared to small bowel mucosal morphology; intraepithelial lymphocytes; and serum endomysial (EmA), reticulin, tissue transglutaminase (anti-tTG) and gliadin antibodies. RESULTS: Of the 59 patients evincing only minor small bowel mucosal changes or positive celiac disease serology, 22 (37%) were negative for DQ2 and DQ8. All EmA-positive patients had celiac-type HLA, but antireticulin antibody, anti-tTg, and antigliadin antibody were also present in HLA-DQ2- and -DQ8-negative individuals. Eleven of 17 patients (65%) observing a gluten-free diet before small bowel biopsy did not share celiac-type HLA. None of the 17 had apparent villous atrophy. Serum EmA and anti-tTG were negative in all. HLA-DQ typing is less expensive than follow-up biopsy in the exclusion of celiac disease. CONCLUSIONS: HLA-DQ2 and -DQ8 determination is useful in exclusion, probably lifelong, of celiac disease in individuals with an equivocal small bowel histological finding. The low specificity of this test must, however, be borne in mind.     

Narrow band imaging combined with water immersion technique in the diagnosis of celiac disease

BackgroundThe “multiple-biopsy” approach both in duodenum and bulb is the best strategy to confirm the diagnosis of celiac disease; however, this increases the invasiveness of the procedure itself and is time-consuming.AimTo evaluate the diagnostic yield of a single biopsy guided by narrow-band imaging combined with water immersion technique in paediatric patients.MethodsProspective assessment of the diagnostic accuracy of narrow-band imaging/water immersion technique-driven biopsy approach versus standard protocol in suspected celiac disease.ResultsThe experimental approach correctly diagnosed 35/40 children with celiac disease, with an overall diagnostic sensitivity of 87.5% (95% CI: 77.3–97.7). An altered pattern of narrow-band imaging/water immersion technique endoscopic visualization was significantly associated with villous atrophy at guided biopsy (Spearman Rho 0.637, p < 0.001). Concordance of narrow-band imaging/water immersion technique endoscopic assessments was high between two operators (K: 0.884). The experimental protocol was highly timesaving compared to the standard protocol.ConclusionsAn altered narrow-band imaging/water immersion technique pattern coupled with high anti-transglutaminase antibodies could allow a single guided biopsy to diagnose celiac disease. When no altered mucosal pattern is visible even by narrow-band imaging/water immersion technique, multiple bulbar and duodenal biopsies should be obtained.     

Successful infliximab treatment for steroid-refractory celiac disease: a case report

Celiac disease is a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. The majority of patients responds to a gluten-free diet but a small number do not. After the exclusion of gluten in the diet, ulcerative jejunititis, and an enteropathy-associated T-cell lymphoma, another treatment modalities, such as systemic steroids and immunosuppressives, may be necessary. This article reports the case of a 47-year-old white woman with immunoglobulin A deficiency. She was diagnosed with celiac disease with subtotal villous atrophy on jejunal biopsy together with positive antiendomysium and antigliadin immunoglobulin G antibodies. Despite close adherence to a gluten-free diet, her weight continued to decrease, she had diarrhea, and her distal duodenal histology showed no improvement. Some improvement in her symptoms was observed with cyclosporine and systemic steroids, but this was not sustained. Recent evidence has suggested that anti-tumor necrosis factor alpha antibodies have a role in the amelioration of an animal model of villous atrophy, and after careful consideration, she was treated with infliximab. There was a dramatic improvement in her weight, symptoms, and distal duodenal histology. The response has been maintained for 18 months while on azathioprine therapy. It is concluded that infliximab is an effective treatment that may be considered in a small number of patients with refractory celiac disease, resistant to other therapy.     

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.     

Chronic unexplained hypertransaminasemia may be caused by occult celiac disease

In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained hypertransaminasemia in comparison with that in the general population (0.5%), 140 consecutive patients with chronic increases of serum transaminases levels of unknown cause were tested for antigliadin and antiendomysium IgA antibodies. All patients with positive antibody tests were offered upper gastrointestinal endoscopy with distal duodenal biopsy. Thirteen patients (9.3%, 95% confidence interval 5. 0-15.4) had positive antigliadin and antiendomysium antibodies. The prevalence of antibodies was 17% in women and 5.4% in men (8/47 vs. 5/93 respectively; relative risk 3.2, 95% confidence interval 1.1-9. 1). Distal duodenal biopsy performed in all but one of the patients showed mild villous atrophy with increased intraepithelial lymphocytes in three cases, subtotal villous atrophy in six, and total villous atrophy in three. The prevalence of celiac disease in the patient group was significantly higher than that in the general population (P <.001) with a relative risk of 18.6 (95% confidence interval 11.1-31.2). On the basis of the present findings, screening for celiac disease is an important tool in the initial diagnostic work-up of patients with chronic unexplained hypertransaminasemia.