Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase antibody for the diagnosis of celiac disease.

BACKGROUND & AIMS: The diagnosis of celiac disease often relies on the anti-tissue transglutaminase (tTG) antibody test. The aim of this study was to evaluate its sensitivity and specificity in clinical practice with the use of commercial laboratories, in which the test characteristics might differ from research laboratories. METHODS: We identified 122 patients with suspected celiac disease who had anti-tTG antibody serologies as well as upper endoscopy with duodenal biopsies. Those with celiac disease were classified as either classic (with diarrhea or other symptoms of malabsorption) or silent (asymptomatic). Biopsies from celiac disease patients were classified as either partial (Marsh IIIA) or total (Marsh IIIB or IIIC) villous atrophy. RESULTS: The overall sensitivity, specificity, and positive and negative predictive values of the anti-tTG antibody test were 70.6%, 65.0%, 91.1%, and 30.2%, respectively. The sensitivity was 90.0% for patients with total villous atrophy and 42.3% for patients with partial villous atrophy (P < .0001). There were differences in both sensitivity and specificity between the 2 most commonly used commercial laboratories. The sensitivity for Lab #1 was 40.0% versus 86.4% for Lab #2 (P < .0001). The specificity for Lab #1 was 100.0%, and it was 41.7% for Lab #2 (P = .02). CONCLUSIONS: The sensitivity of the anti-tTG antibody in clinical practice is not as high as previously reported in research laboratories. The sensitivity is significantly lower in patients with partial villous atrophy. There is also significant variability in test characteristics among major commercial laboratories in the United States. These results need to be confirmed in prospective studies.     

Correlation of Clinical and Histopathological with Endoscopic Findings of Celiac Disease in the Turkish Population

Endoscopic findings have been described for the diagnosis of celiac disease but the relationship amond the clinical presentation, endoscopic markers, and the degree of histopathological findings is not clear. Thirty patients who were thought to have celiac disease were included in this study. Biopsies taken from the duodenum were examined histopathologically. The relationship among the endoscopic, clinical, and histopathological findings were investigated. Partial villous atrophy was seen in 14 patients (46.6%), and subtotal and total villous atrophy were seen in 6 (20%) patients each. Eighty six percent of patients with a mosaic appearance, 76% of patients with the finding of loss of folds, and 90% of patients with scalloping on endoscopy had either partial villous atrophy, subtotal villous atrophy, or total villous atrophy on biopsy. We conclude that endoscopic findings in celiac disease can reveal valuable information both for diagnosis and for demonstration of the severity of the disease state.     

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice

OBJECTIVE: We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives. METHODS: The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy). RESULTS: The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA. CONCLUSIONS: Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.     

Endomysial antibody: is it the best screening test for coeliac disease?

The sensitivities and specificities of the IgA and IgG antigliadin antibody and the IgA antireticulin antibody have been compared with the recently described endomysial antibody directed against the basement membrane of smooth muscle in monkey oesophagus. One hundred and seventeen patients with adult coeliac disease (21 untreated), 84 patients with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis (comprising the disease control group), 47 normal controls and a miscellaneous group of 29 patients, who were selected because of a positive reticulin staining pattern, were investigated. These results were correlated with the degree of abnormality of the intestinal mucosa in patients with adult coeliac disease. Endomysial antibodies were found in all patients with untreated coeliac disease and subtotal villous atrophy and in 47% of patients on a non-strict gluten free diet. One patient on a strict gluten free diet was positive and had partial villous atrophy while all patients in disease control groups were negative. Results were variable with the antireticulin and antigliadin antibodies. Sensitivity and correlation with subtotal villous atrophy in the untreated patients was 100%. It is concluded that the endomysial antibody is superior to other current antibody tests and should be used in preference for the diagnosis of coeliac disease.     

The Role of Capsule Endoscopy in Suspected Celiac Disease Patients with Positive Celiac Serology

Background  

Endomysial antibody (EMA) and tissue transglutaminase (tTG) antibody testing is used to screen subjects with suspected celiac disease. However, the traditional gold standard for the diagnosis of celiac disease is histopathology of the small bowel. As villous atrophy may be patchy, duodenal biopsies could potentially miss the abnormalities. Capsule endoscopy can obtain images of the whole small intestine and may be useful in the early diagnosis of celiac disease.     

Adult celiac disease with severe or partial villous atrophy: a comparative study

BACKGROUND AND AIMS: While severe villous atrophy (SVA) is the most typical histological feature in adult celiac disease (ACD), partial villous atrophy (PVA) is now also frequently found. So far, the impact of the severity of villous atrophy on the clinical presentation of ACD has been scarcely investigated. We aimed to compare the clinical, biological and immune features and outcomes in ACD patients presenting with PVA at diagnosis versus patients with SVA. PATIENTS AND METHODS: Medical files of 48 patients with ACD diagnosed between 1992 and 2003 were retrospectively studied. The diagnosis was based on the presence of intestinal villous atrophy, with increases in intraepithelial lymphocytes and circulating celiac specific antibodies. Villous atrophy was classified as severe (subtotal and total) or partial. Symptoms, biological signs of malabsorption, immune markers, bone mineral density at diagnosis and response to gluten-free diet were recorded. RESULTS: At diagnosis, ten patients (four M/six F) had PVA and 38 patients (five M/33 F) had SVA, with a median age of 54 and 33 years, respectively (p<0.05). Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both PVA and SVA patients, as was their response to gluten-free diet. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy. CONCLUSION: PVA was observed in 21% of patients with ACD. Except for their older age at diagnosis, patients with PVA presented with similar clinical, biological and immune characteristics and outcomes as did patients with SVA.     

Endoscopic features of celiac disease in children.

BACKGROUND: Endoscopic abnormalities have been described in adult patients with celiac disease that may suggest the diagnosis, especially when the presentation is atypical. METHODS: The duodenum of 140 children undergoing EGD for various different indications was evaluated macroscopically and histologically. RESULTS: Histology revealed total villous atrophy in 80 patients, 79 of whom had celiac disease. Among these, 100% had a mucosal mosaic pattern in the duodenum (sensitivity 98.7%, specificity 96.7%, positive predictive value 97.5%, negative predictive value 98.3%), 70% had scalloped duodenal folds (sensitivity 68.7%, specificity 98.3%, positive predictive value 98.2%, negative predictive value 70.2%), 15% had visible vasculature, and 6% had reduction of duodenal folds. Sensitivity and specificity of endoscopic findings were not modified by chromoendoscopy. Except for the mosaic pattern, the frequency of endoscopic abnormalities increased with age; reduction of duodenal folds was never seen in children with celiac disease who were less than 5 years of age. CONCLUSIONS: The frequency and diagnostic value of endoscopic abnormalities are different in children with celiac disease compared with adults with this disease. Because indications for endoscopy, such as abdominal pain, dyspepsia, and unexplained anemia, can be manifestations of celiac disease, and villous atrophy may have a patchy distribution, awareness of these endoscopic abnormalities is important in the diagnosis of celiac disease in children.     

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.     

Diagnosis and therapy of celiac disease in adolescence and adulthood

The incidence of celiac disease has increased considerably during the last two decades. Celiac Disease is now diagnosed in adults at least as frequently as in children. A prevalence of about 1:200 seems reasonable in central Europe. Besides the typical symptomatic presentation, silent, latent and potential celiac disease are found. Oligo- to asymptomatic courses (silent celiac disease) are increasingly found in all age groups. Endomysial antibodies and tissue-transglutaminase antibodies are sensitive and specific for about 95% of celiac patients. However, the final diagnosis is only done by a - mostly endoscopical - biopsy from the distal part of the duodenum, demonstrating hyperplastic villous atrophy of the mucosa with increased numbers of intraepithelial lymphocytes. The biopsies should be classified histologically according to the modified Marsh criteria. Increased prevalence in family members (10 to 15%) and in associated diseases (e.g. diabetes mellitus) lead to the recommendation of active screening in populations at risk. Although the clinical symptoms are rather variable and different, the response to a lifelong strict gluten free diet is nearly 100%. So-called refractory celiac disease is very rare. There are numerous associated diseases as dermatitis herpetiformis, diabetes mellitus type I, thyroid and neurologic diseases. The most frequent complications are retardation of growth in childhood, early onset osteoporosis, and an increased risk of abortions. The most severe complication is intestinal lymphoma. Especially patients with late diagnosis and bad dietary adherence are at risk. A regular follow-up of patients, rather with antibody tests than with duodenal biopsies is recommended to test and secure dietary compliance.     

Disappointing sensitivity of endoscopic markers for villous atrophy in a high-risk population: implications for celiac disease diagnosis during routine endoscopy

OBJECTIVE: Endoscopic markers of duodenal villous atrophy (VA) can facilitate diagnosis of celiac disease during routine upper GI endoscopy. We studied their sensitivity for VA in a large series of patients undergoing GI endoscopy specifically for duodenal biopsy. Poor sensitivity in this setting would have significant and adverse implications for their performance during routine endoscopy. METHODS: All patients with VA on duodenal biopsy performed for positive serum endomysial antibody (EmA) and/or clinical features suggestive of celiac disease were included. The second part of duodenum was inspected carefully for endoscopic markers using videogastroscopes. RESULTS: Of 129 patients studied, 99 (77%) had at least one endoscopic markers. The most commonly seen marker were a mosaic pattern mucosa (68 patients, 53%) and scalloping of duodenal folds (74 patients, 57%). The prevalence of markers was significantly lower for partial VA (15 of 26 patients, 58%) than for subtotal or total VA (84 of 103 patients, 82%) (p < 0.02). CONCLUSIONS: Endoscopic markers have disappointing sensitivity even in a population at high risk of celiac disease, particularly for partial VA. Their performance may be even poorer in an unselected dyspeptic population. Although they may help improve diagnosis rates among patients with nonspecific dyspeptic symptoms, many patients, particularly those with milder enteropathy, will be missed. As celiac disease is an important cause of dyspepsia, consideration should be given to serological screening to further improve diagnosis rates, as few centers will have the resources to routinely biopsy all patients.     

Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation

AIM: To investigate the association between serum antibody levels and a subsequent celiac disease diagnosis in a large series of children and adults.METHODS: Besides subjects with classical gastrointestinal presentation of celiac disease, the study cohort included a substantial number of individuals with extraintestinal symptoms and those found by screening in at-risk groups. Altogether 405 patients underwent clinical, serological and histological evaluations. After collection of data, the antibody values were further graded as low [endomysial (EmA) 1:5-200, transglutaminase 2 antibodies (TG2-ab) 5.0-30.0 U/L] and high (EmA 1: ≥ 500, TG2-ab ≥ 30.0 U/L), and the serological results were compared with the small intestinal mucosal histology and clinical presentation.RESULTS: In total, 79% of the subjects with low and 94% of those with high serum EmA titers showed small-bowel mucosal villous atrophy. Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a gluten-containing diet, or responded positively to a gluten-free diet.CONCLUSION: Irrespective of the initial serum titers or clinical presentation, EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis.     

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.     

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.     

T lymphocyte populations of the intestinal mucosa in celiac disease in children. Immunohistochemical study

In order to study the distribution of lymphocyte subpopulations in a pathologic intestinal mucosa, the authors, instead of using the classic method by counting the number of lymphocytes, present an original method permitting the exploitation of quantified data from labelled surface cells by texture analyser coupled with a computerized system. We investigated 25 children presenting with chronic diarrhea and villous atrophy and 5 control subjects. Fifteen of the 25 children had celiac disease (10 active with total villous atrophy and 5, celiac disease in remission with healing mucosa), 5 cow's milk protein intolerance with total or partial villous atrophy and 5, chronic diarrhea with partial villous atrophy. Immunohistochemical study with monoclonal antibodies was carried out on frozen sections using a three-step immunoperoxidase technique. Compared with the 5 controls, patients with food intolerance (celiac disease and cow's milk protein intolerance) showed a significant increase of T suppressor lymphocytes (p less than 0.01 and p less than 0.05) in the epithelium, whereas there were more T helper lymphocytes in the lamina propria (p less than 0.05 and p less than 0.01). Non-treated celiac disease was distinguished from treated celiac disease by a marked increase in intra-epithelial T cytotoxic-suppressors. These results suggest that T cytotoxic-suppressors may be the mediators of the lesions observed in celiac disease.     

Morphometric Analysis of Small-Bowel Mucosa in Turkish Children with Celiac Disease and Relationship with the Clinical Presentation and Laboratory Findings

We aimed to analyze morphometric features of the small-bowel mucosa in children with celiac disease, to assess the diagnostic limit values of morphometric findings, and to examine the association of morphometric findings with the clinical presentation and laboratory findings. The study comprised 33 patients with celiac disease and 35 pediatric patients undergoing endoscopy for other causes. Biopsy specimens were reanalyzed for (1) intraepithelial lymphocytes, (2) goblet cells, (3) villous height, and (4) villous/crypt ratio. The morphometric parameters of the patients were compared with controls. Then celiac patients were divided into two groups according to the presence of total villous atrophy and clinical and laboratory findings were compared. Histologic examination revealed that goblet cells, villus height, and villous/crypt ratio were significantly lower and intraepithelial lymphocytes were significantly higher in celiac patients. Cutoff values for intraepithelial lymphocytes and goblet cells in celiac patients were 31/100 and 7.8/100 epithelial cells, respectively. Moreover, for villus height and villous/crypt ratio, cutoff values were 633 μm and 0.72, respectively. Serum folic acid and vitamin B₁₂ levels were significantly lower in patients with total villous atrophy and were positively correlated with the severity of villous atrophy. We suggest that morphologic examination and laboratory data are important for definitive diagnosis. Villous/crypt ratio is the most sensitive and specific parameter, and intraepithelial lymphocytes may be used along with villous/crypt ratio, especially in the early phase. Folic acid and vitamin B₁₂ levels are good indicators of villous atrophy.     

Duodenal biopsy may be avoided when high transglutaminase antibody titers are present

AIM： To evaluate the predictive value of tissue transglutaminase （tTG） antibodies for villous atrophy in adult and pediatric populations to determine if duodenal biopsy can be avoided. METHODS： A total of 324 patients with celiac disease （CD; 97 children and 227 adults） were recruited prospectively at two tertiary centers. Human IgA class anti-tTG antibody measurement and upper gastrointestinal endoscopy were performed at diagnosis. A second biopsy was performed in 40 asymptomatic adults on a gluten-free diet （GFD） and with normal tTG levels. RESULTS： Adults showed less severe histopathology （26% vs 63%; P 〈 0.0001） and lower tTG antibody titers than children. Levels of tTG antibody correlated with Marsh type in both populations （r = 0.661; P 〈 0.0001）. Multiple logistic regression revealed that only tTG antibody was an independent predictor for Marsh type 3 lesions, but clinical presentation type and age were not. A cut-off point of 30 U tTG antibody yielded the highest area under the receiver operating characteristic curve （0.854）. Based on the predictive value of this cut-off point, up to 95% of children and 53% of adults would be correctly diagnosed without biopsy. Despite GFDs and decreased tTG antibody levels, 25% of the adults did not recover from villous atrophy during the second year after diagnosis. CONCLUSION： Strongly positive tTG antibody titers might be sufficient for CD diagnosis in children. However, duodenal biopsy cannot be avoided in adults because disease presentation and monitoring are different.     

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.     

Effect of a gluten-free diet on growth and small-bowel histology in children with celiac disease in India

BACKGROUND AND AIM: Follow-up studies on growth and histological recovery of children with celiac disease (CD) while on a gluten-free diet (GFD) are lacking from Asia. We therefore assessed the effects of this diet. METHODS: Forty-two children with CD were enrolled. Weight and height were expressed as weight for height (WfH) and height standard deviation scores (HSDS), respectively. Twenty-five children had repeated duodenal biopsies after 1-2 years and 14 had a third biopsy after 3-7 years of GFD. Compliance was checked by regular interview and IgA antiendomysial antibody estimation (EMA). RESULTS: At diagnosis (n = 25), mean HSDS was -3.3 +/- 1.6 with 76% having a HSDS of <-2; 60% were undernourished (WfH mean 81.6 +/- 5.7). Over a mean follow up of 3.7 years, HSDS improved to -1.3 +/- 1.7 and 84% cases achieved normal nutrition. Mean height velocity was 13.9 cm during first year and 5.6 cm in subsequent years. Small-bowel biopsies at diagnosis showed subtotal villous atrophy (Marsh IIIb) in 18 (72%) and partial villous atrophy (Marsh IIIa) in seven (28%) patients. Repeat biopsy at 1-2 years showed shift from subtotal to partial villous atrophy in 94% (n = 17/18) and normalization in one patient. In patients with Marsh IIIa improvement of partial villous atrophy was observed in all. Immunoglobulin A endomysial antibody was negative in 81%. Repeat biopsies at 5 years of GFD showed improvement to Marsh I-II, but none normalized. CONCLUSION: The majority of children with CD show normalization of nutrition and growth after GFD. Small-bowel histology improves markedly but does not normalize even after 5 years of GFD.     

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.     

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.