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.     

Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis.

Serum IgA antiendomysial antibodies (EmA) were present in 20 (64.5%) of 31 patients with dermatitis herpetiformis (DH) on a normal diet. A significant correlation was found between these antibodies and the severity of gluten-induced jejunum damage. IgA EmA were positive in 19 (86%) of the 22 DH patients with subtotal villous atrophy, in comparison with the positivity of only one (11%) of the nine DH patients with less severe intestinal involvement (partial villous atrophy or mild abnormalities). The specificity of this test for gluten-sensitive enteropathy was 100%, these antibodies being consistently negative in biopsied disease controls showing a normal jejunal mucosa. Moreover, IgA EmA proved to be useful in monitoring the response to gluten withdrawal in DH patients, as these antibodies always disappeared in all the DH cases studied after 1 year of gluten-free diet together with the regrowth of jejunal villi. The strict relationship between IgA EmA and subtotal villous atrophy is more helpful still since the enteropathy present in DH is usually symptomless and therefore difficult to suspect.     

Sorbitol H2-breath test versus anti-endomysium antibodies to assess histological recovery after gluten-free diet in coeliac disease.

Background. Gluten-free diet plays a key role in treatment of coeliac disease, but it is difficult to evaluate its effect on improvement of villous architecture using sensitive non-invasive tests.

Aims. To compare sorbitol H₂-Breath Test with antiendomysial antibodies in the follow-up of coeliac disease to detect histological recovery.

Methods. A total of 38 consecutive patients with coeliac disease were studied. All underwent Sorbitol H₂-Breath Test, antiendomysial and oesophagogastroduodenoscopy with multiple bioptic samples before diet and then 6, 12 and 18 months after gluten-free diet. Expiratory samples were collected before patients drank the test solution (5 g sorbitol in 150 ml tap water) and thereafter every 30 min for 4 hours. An increase in H₂ concentration of ≥20 ppm, above fasting baseline was considered positive for sorbitol malabsorption. Antiendomysial antibodies were evaluated by the indirect immunofluorescent method.

Results. Antiendomysial antibodies were positive in 32/38 patients before gluten-free diet (84.21%), while they were positive in 20/34 (54.82%), 2/16 (12.5916) and 0/2 (0%) cases after 6, 12 and 18 months of gluten-free diet, respectively, no correlation being found with improvement of histological lesions (p=ns). As far as concerns sorbitol H₂-Breath Test, maximal cut-off value (in ppm) decreased progressively and parallel to histological recovery during follow-up. Indeed, it decreased from a mean 63 ppm before diet to 35, 19 and 12 ppm, after 6, 12 and 18 months of gluten-free diet, with a statistical difference being found before and after [p<0.001]. Likewise, the peak value (in minutes) appeared progressively later during follow-up, parallel to histological recovery. In fact, it appeared at a mean of 119 minutes before gluten-free diet, while it appears at a mean of 164, 195 and 219 minutes after 6, 12 and 18 months on glutenfree diet. A statistical difference before and after start of gluten-free diet was found also in this case (p<0.001). Conclusions. Sorbitol H2-Breath Test is better than antiendomysial antibodies in revealing histological recovery in the follow-up of coeliac patients after the start of gluten-free diet due to its good correlation with histological damage. Moreover, it also appears to be able to detect dietary mistakes of the patients on gluten-free diet.     

Sorbitol H2-breath test versus anti-endomysium antibodies for the diagnosis of subclinical/silent coeliac disease.

BACKGROUND: Recent studies have shown that the prevalence of anti-endomysial antibodies (EMAs) in clinical practice is lower than expected; the aim of our study was therefore to compare the sorbitol H2-breath test (BT) with EMAs in the diagnosis of subclinical/silent coeliac disease and to compare with histologic lesions. METHODS: We studied 123 consecutive patients with subclinical (96) and silent (27) coeliac disease. Expiratory samples were collected before the patients drank the test solution (5 g of sorbitol in 150 ml of tap water) and every 30 min for 4 h. An increase in H2 concentration of at least 20 ppm over fasting baseline was considered positive for sorbitol malabsorption. EMAs were screened by the indirect immunofluorescence method. RESULTS: EMAs were positive in 77/96 (80.80%) and sorbitol H2-BT in 94/96 (97.91%) patients with subclinical coeliac disease, while EMAs were positive in 17/27 (62.96%) and sorbitol H2-BT in 26/27 (96.29%) patients with silent coeliac disease (P < 0.001 in both forms of coeliac disease). The best cut-off values in ppm and minutes are higher and shorter in the severe form than in the minor form of intestinal damage, respectively (P < 0.001 in both forms). CONCLUSIONS: This study indicates that almost all subclinical/silent coeliac patients show abnormal sorbitol H2-BT and that there is a strict correlation between cut-off value (in ppm and minutes) and histologic lesions. In particular, the maximal cut-off value (in ppm and in minutes) correlates statistically with the more severe the grade of intestinal damage. Finally, the prevalence of EMA in subclinical/silent disease is lower than expected.     

Association of FAS （TNFRSF6）-670 gene polymorphism with villous atrophy in coeliac disease

AIM:To investigate the association of FASgene polymorphism with coeliac disease (CD) development.METHODS: FAS-G670A gene polymorphism, located in a gamma interferon activation site, was studied in 146 unrelated CD patients and 203 healthy ethnically matched controls. The restriction fragment length polymorphism (RFLP) method was used to identify FAS-G670A gene polymorphism.RESULTS:No significant difference was found in genotype frequency between CD cases and controls. In controls,however, the frequency of the GGgenotype was significantly higher in women (26.5%) than in men (12.8%) (OR=2.44,95% CI1.15-5.20, P=0.020) and it was also higher in men with CD than controls (OR=2.60, 95% (CI0.96-7.05, P=0.061).The GG genotype frequency was significantly higher in patients with most severe villous atrophy (Marsh Ⅲc lesions) (OR=3.74, 95% CI 1.19-11.82, P=0.025). A significantly less proportion of men suffered from Marsh IIIc lesions than women (OR=0.20, 95% (CI0.06-0.68, P=0.01). The risk of having severe villous atrophy increased with the additive effect of the Gallele in women (P=0.027 for trend, age and gender adjusted).CONCLUSION: FAS-G670A gene polymorphism is associated with the severity of villous atrophy in CD. Female gender is also associated with the severity of villous atrophy.     

Screening for celiac disease in Tunisian patients with Graves' disease using anti-endomysium and anti-tissue transglutaminase antibodies

OBJECTIVE: Celiac disease (CD) can be associated with autoimmune thyroid diseases. The aim of this study was to screen for CD in patients with Graves' disease in Tunisia. PATIENTS AND METHODS: Sera from 161 patients with Graves' disease were tested for IgA class anti-endomysium antibodies (AEA) using indirect immunofluorescence on cryostat sections of human umbilical cord and for IgA class anti-human tissue transglutaminase antibodies (AtTG) by ELISA. RESULTS: AEA were positive in 6 out of 161 (3.7%) patients with Graves' disease and all 6 patients were also positive for AtTG. Four of these 6 patients with positive serological markers of CD underwent duodenal biopsy; three had marked villous atrophy, one has normal histological picture and two did not agree to undergo biopsy. The prevalence of biopsy confirmed CD in patients with Graves' disease was 1.86% (3/161). CONCLUSION: Patients with Graves' disease are at substantial risk of CD and therefore antibody screening for CD may be included in the work-up of these patients. Either AEA or AtTG may be used.     

A comparison study between Magniview and high definition white light endoscopy in detecting villous atrophy and coeliac disease: A single centre pilot study

Background and aimsCoeliac disease may be missed at gastroscopy. We aimed to assess the sensitivity of Pentax optical zoom technology endoscopes in detecting duodenal villous atrophy and the ease of image interpretation by non-coeliac specialists.MethodAll patients attending for a gastroscopy were assessed for endoscopic villous atrophy in part one and two of the duodenum with high definition white light endoscopy and magnification endoscopy. Endoscopic findings of the duodenum were compared to histology as the reference standard.A short training video of varying degrees of villous atrophy seen by magnification endoscopy was used to train individuals. They were then assessed for the ability to differentiate between normal duodenum and villous atrophy.ResultsTwo hundred and fifty patients were prospectively recruited (145 females, 58%; age range 16–84, median age 50.5). Ninety-six patients had villous atrophy on histology (38.4%) 154 were controls. Magnification endoscopy had a higher sensitivity in detecting villous atrophy compared to high definition white light endoscopy (86.4% versus 78.4%, p = .0005).9/10 individuals undertaking magnification endoscopy training correctly identified all cases of villous atrophy.ConclusionMagnification endoscopy has superior diagnostic sensitivity in detecting villous atrophy compared to high definition white light endoscopy and the potential to be easily adopted by all endoscopists.     

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.     

Sorbitol H2-breath test versus anti-endomysium antibodies to assess histological recovery after gluten-free diet in coeliac disease

Background. Gluten-free diet plays a key role in treatment of coeliac disease, but it is difficult to evaluate its effect on improvement of villous architecture using sensitive non-invasive tests.Aims. To compare sorbitol H₂-Breath Test with antiendomysial antibodies in the follow-up of coeliac disease to detect histological recovery.Methods. A total of 38 consecutive patients with coeliac disease were studied. All underwent Sorbitol H₂-Breath Test, antiendomysial and oesophagogastroduodenoscopy with multiple bioptic samples before diet and then 6, 12 and 18 months after gluten-free diet. Expiratory samples were collected before patients drank the test solution (5 g sorbitol in 150 ml tap water) and thereafter every 30 min for 4 hours. An increase in H₂ concentration of ≥20 ppm, above fasting baseline was considered positive for sorbitol malabsorption. Antiendomysial antibodies were evaluated by the indirect immunofluorescent method.Results. Antiendomysial antibodies were positive in 32/38 patients before gluten-free diet (84.21%), while they were positive in 20/34 (54.82%), 2/16 (12.5916) and 0/2 (0%) cases after 6, 12 and 18 months of gluten-free diet, respectively, no correlation being found with improvement of histological lesions (p=ns). As far as concerns sorbitol H₂-Breath Test, maximal cut-off value (in ppm) decreased progressively and parallel to histological recovery during follow-up. Indeed, it decreased from a mean 63 ppm before diet to 35, 19 and 12 ppm, after 6, 12 and 18 months of gluten-free diet, with a statistical difference being found before and after [p<0.001]. Likewise, the peak value (in minutes) appeared progressively later during follow-up, parallel to histological recovery. In fact, it appeared at a mean of 119 minutes before gluten-free diet, while it appears at a mean of 164, 195 and 219 minutes after 6, 12 and 18 months on glutenfree diet. A statistical difference before and after start of gluten-free diet was found also in this case (p<0.001). Conclusions. Sorbitol H2-Breath Test is better than antiendomysial antibodies in revealing histological recovery in the follow-up of coeliac patients after the start of gluten-free diet due to its good correlation with histological damage. Moreover, it also appears to be able to detect dietary mistakes of the patients on gluten-free diet.     

Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study

OBJECTIVE: In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy. MATERIAL AND METHODS: Forty-one adults suspected of coeliac disease owing to increased density of mucosal gamma(delta)+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls. RESULTS: Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects. CONCLUSIONS: Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.     

Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: A prospective and randomized clinical study

Objective In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy.

Material and methods Forty-one adults suspected of coeliac disease owing to increased density of mucosal γδ+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls.

Results Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects.

Conclusions Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.     

An association between primary biliary cirrhosis and jejunal villous atrophy resembling celiac disease

Summary A 76-year-old female presented with malabsorption and was subsequently shown to have jejunal villous atrophy. There was only partial clinical and histologic recovery with gluten withdrawal, but this was thought to be due to poor adherence to the diet. The findings were considered to be consistent with adult celiac disease. During the course of investigations, she was also found to have primary biliary cirrhosis. This is the fifth recorded instance of this association and the first from North America. Because these are uncommon conditions, it is postulated that this is unlikely to be a chance association. The recognition of this coexistence is of practical importance in the investigation and treatment of patients with primary biliary cirrhosis and celiac disease.     

IgA antibodies to gliadin and coeliac disease in psoriatic arthritis.

OBJECTIVES: To find out whether patients with psoriatic arthritis (PsoA) have an increased prevalence of antibodies to gliadin (AGA) and of coeliac disease. METHODS: One hundred and fourteen PsoA patients with skin disease of 20+/-13 yr and joint disease of 11+/-10 yr duration answered a questionnaire concerning their medical history and underwent clinical examination, including radiology. Serum IgA AGA and IgG AGA, IgA antibodies to endomysium and immunoglobulins, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration were determined. RESULTS: Five of the 114 patients (4.4%) had coeliac disease. After exclusion of these five patients, the mean IgA AGA concentration was significantly higher (P=0.0005) than that in a reference group. None of the patients had IgA antibodies to endomysium. The mean serum IgA concentration was significantly increased and IgM decreased. Patients with a high concentration of IgA AGA had significantly higher ESR and CRP and a longer duration of morning stiffness than those with a low AGA concentration. CONCLUSIONS: Patients with PsoA have an increased prevalence of raised serum IgA AGA and of coeliac disease. Patients with raised IgA AGA seem to have more pronounced inflammation than those with a low IgA AGA concentration.     

Reticulin antibodies in patients with coeliac disease and their relatives.

The sera of 69 index coeliac patients, 121 of their first-degree relatives, and 104 controls were screened for the presence of reticulin antibodies. Among the untreated coeliac patients 75% of adults and 93% of children had reticulin antibody in their serum. Reticulin antibody was not present in any adequately treated coeliac patient. Of the first-degree relatives, 21 were reticulin antibody positive; 17 of these were biopsied and 12 were shown to have coeliac disease. Sixty-five of the coeliac relatives who did not have reticulin antibodies in their sera were biopsied and two had coeliac disease. Of the 68 relatives and 63 controls with normal biopsies, five of the relatives and four of the controls were reticulin antibody positive.     

Endomysium antibodies in coeliac disease: an improved method.

The ultra structural binding sites of endomysium antibodies have been studied on human umbilical cord tissue. The sensitivity and specificity of IgA endomysium antibodies were compared with recently described methods using basement membrane of smooth muscle of monkey oesophagus. Thirty adults affected by coeliac disease (10 in remission) and 75 healthy adult controls with normal intestinal mucosa (35 false antigliadin positive) were investigated. Sensitivity and correlation of endomysium antibodies with total villous atrophy in untreated coeliac disease patients were 100% on the human umbilical cord smooth muscles, and only 90% on the muscular layer of primate oesophagus. Indirect immunofluorescence was superior to peroxidase staining in detecting these IgA antibodies. The easy availability and enhanced testing sensitivity of the umbilical cord is an advance towards a better diagnostic tool for coeliac disease.     

Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease

OBJECTIVE: Endomysial antibodies (EMA) are a well-known hallmark of celiac disease, but some recent studies showed that the prevalence of these antibodies in clinical practice is lower than expected. The aim of our study was to determine the prevalence of antigliadin (AGA) and EMA antibodies on a consecutive series of subclinical/silent celiac patients. METHODS: We studied 115 consecutive patients with subclinical (92 patients) or silent (23 patients) forms of celiac disease. AGA and EMA were screened in all patients. Histopathology of celiac disease was expressed according to the Marsh classification. RESULTS: The overall AGA in subclinical form were positive in 77% (14 of 18) of patients with partial villous atrophy (VA), in 84% (21 of 25) of patients with subtotal VA, and in 90% (27 of 30) of patients with total VA, whereas EMA were positive in 88.88% (16 of 18) of patients with partial VA, in 92% (23 of 25) of patients with subtotal VA, and 96.66% (29 of 30) of patients with total VA. On the other hand, AGA were positive in 0% (zero of two) of patients with Marsh I and in 30% (three of 10) of patients with Marsh II, whereas EMA were positive in 0% (zero of two) of patients with Marsh I and in 40% (four of 10) of patients with Marsh II (Marsh I-IIIa vs Marsh IIIb-c, p = < 0.005 in overall AGA-positive patients and p = < 0.0001 in EMA-positive patients). At the same time the overall AGA in silent form were positive in 60% (three of five) of patients with partial VA, in 66.66% (four of six) of patients with subtotal VA, and in 77.77% (seven of nine) of patients with total VA, whereas EMA were positive in 80% (four of five) of patients with partial VA, in 83.33% (five of six) of patients with subtotal VA, and in 88.88% (eight of nine) of patients with total VA. On the other hand, overall AGA were positive in 0% of patients with both Marsh I (zero of one) and Marsh II (zero of two), as well as EMA were positive in 0% with both Marsh I (zero of one) and Marsh II (zero of two) (Marsh I-IIIa vs Marsh IIIb-c, p = < 0.001 in overall AGA-positive patients and p = < 0.007 in EMA-positive patients). CONCLUSIONS: At this time small bowel biopsy seems to be the only correct procedure to diagnose a case of suspected celiac disease, especially in patients with mild symptoms or suspected for celiac disease, because they belong to high-risk groups.