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PubMed2000

The measurement of IgA and IgG transglutaminase antibodies in celiac disease: a comparison with current diagnostic methods.

Celiac disease (CD) is an inflammatory disorder of the small intestine induced by cereal prolamins. The demonstration of IgA endomysial antibodies (EMA) is currently the most reliable serological screen for CD. The antigenic target is transglutaminase. The aim of this study was to develop an ELISA assay for the detection of antibodies to transglutaminase (TGA), and to assess the sensitivity and specificity of TGA for the detection of celiac disease against the benchmarks of jejunal biopsy, antigliadin antibodies (AGA) and EMA. Sera from 57 patients with celiac disease were tested for IgA and IgG TGA, IgA EMA, IgA and IgG AGA, and the total IgA level. The sensitivity, specificity, predictive value and concordance of AGA, EMA and TGA were assessed against the gold-standard biopsy result. IgG plus IgA TGA offered 100% sensitivity in CD patients for whom no dietary intervention had been commenced, with a specificity of 61%. The sensitivity of TGA dropped from 100 to 79% after dietary restriction. In patients on no gluten restriction, there was 100% agreement between TGA and EMA, and 100% agreement between TGA and AGA for the IgA isotype. The false-positive rate for TGA was 53% in Down's syndrome patients and 25% in patients with systemic autoimmune disorders. We conclude that testing for TGA is a reliable diagnostic serology for celiac disease, with improved sensitivity compared with established methods. The results suggest that serial TGA measurements may be a more and accurate marker for dietary compliance than AGA, but prospective studies are required.

Autoantibodies↗
PubMed2006

Endoscopic markers of villous atrophy are not useful for the detection of celiac disease in patients with dyspeptic symptoms.

BACKGROUND AND STUDY AIMS: Celiac disease can manifest with nonspecific symptoms, including functional gastrointestinal disorders such as dyspepsia. The aim of our study was to assess the usefulness of duodenal endoscopic markers of villous atrophy for the selection of dyspeptic patients for histological assessment. PATIENTS AND METHODS: Esophagogastroduodenoscopy was performed in dyspeptic patients, in patients considered to be at risk of having celiac disease, and in healthy controls. At least three duodenal biopsies were performed for histological assessment of villous atrophy in all patients and controls. We looked for the following four duodenal endoscopic markers of celiac disease: reduction in the number of folds, scalloping of folds, mosaic-pattern mucosa, and nodular mucosa. RESULTS: A total of 175 people were enrolled (75 patients with dyspepsia; 75 patients who were "at risk" of having celiac disease; and 25 healthy volunteers, or "controls"). Of the dyspeptic patients, four had endoscopic markers of celiac disease with no histologically confirmed villous atrophy, while one patient without endoscopic markers was found to have Marsh type I villous atrophy. Of the patients at risk of having celiac disease, 16 had at least one endoscopic marker and 10/16 were found to have histological villous atrophy. In this group, the sensitivity and specificity of the endoscopic markers were 100 % and 90.8 % respectively. "At-risk" patients with two or more endoscopic markers all had histologically confirmed villous atrophy. Neither endoscopic markers nor villous atrophy were found in any of the control patients. CONCLUSIONS: Additional endoscopic markers are valuable for diagnosis in patients with clinical symptoms suggestive of celiac disease. In contrast, endoscopic markers of villous atrophy are not useful for selecting a subgroup of dyspeptic patients for screening for celiac disease by duodenal histological assessment. These patients should be screened using other protocols.

Adolescent↗
PubMed2003

Assessment of the DQ heterodimer test in the diagnosis of celiac disease in the Canary Islands (Spain).

BACKGROUND: Celiac disease is a multifactorial disorder of the proximal small intestine associated with a permanent intolerance to gluten. The HLA-DQ(alpha1*0501, beta1*02) heterodimer is strongly associated with this disease. MATERIALS AND METHODS: The authors studied a sample of 354 unrelated Caucasoid individuals: 118 patients with celiac disease and 236 control subjects. All patients and controls subjects were born in Gran Canaria (Canary Islands) at least two generations ago. The authors typed the HLA-DQA1 and DQB1 genes by DNA methods. The positive and negative predictive values of the test were studied. RESULTS: The mean age at diagnosis was 25.4 months, with a statistically significant proportion of females (64.4%, P < 0.002). For DQB1 gene, the susceptibility allele found was DQB1*02 (relative risk [RR] = 7.60, confidence interval [CI]: 5.35-10.78), whereas for the DQA1 gene, the susceptibility alleles found were DQA1*0501 (RR = 2.99, CI: 2.16-4.14) and DQA1*0201 (RR = 1.88, CI: 1.25-2.82). The presence of the DQ(alpha1*0501, beta1*02) heterodimer was strongly associated with the disease (92.4% in the patients group vs. 21.6% in control subjects). HLA-DQ8 heterodimer was absent in the authors' patients. DQB1*02 homozygous subjects presented a higher relative risk for celiac disease. There was no correlation of DQB1*02 dosage with age at onset below 12 years of age or with gender distribution. Sensitivity, specificity, and the positive and negative predictive values of the test were 92.4%, 78.4%, 68.1%, and 95.4%, respectively. CONCLUSIONS: The presence of the DQ2 (DQA1*0501/DQB1*02) heterodimer is strongly associated with celiac disease in the population studied by the authors. The value of this test derives from its ability to exclude disease when a negative result occurs.

Alleles↗
PubMedDate not supplied

[Biochemical markers of bone turnover in children with celiac disease on gluten-free diet].

UNLABELLED: Celiac disease is known to predispose patients to disturbances in bone metabolism. However, little information is available on the biochemical bone turnover markers in celiac children treated with gluten-free diet. AIM: The aim of presented study was to assess bone resorption and formation processes by biochemical bone turnover markers in children with celiac disease on gluten-free diet. SUBJECTS AND METHODS: We studied 20 children with celiac disease (age range 1.5 - 16 yr; 11 girls, 9 boys). The mean age of diagnosis was 2.6 +/- 1.9 yr and the mean duration of gluten-free diet was 7.8 +/-5.1 yr. Results were compared with those obtained in 130 healthy children. Serum levels of bone-specific alkaline phosphatase and osteocalcin as bone formation indices and serum level of C-telopeptide of type I collagen as bone resorption index were measured by immunoenzymatic methods. Additionally, serum vitamin D, calcium and phosphorus were also estimated. RESULTS: Lower median values of C-telopeptide of type I collagen were observed in about 50% tested celiac patients. Some of them also had lower osteocalcin level. However, in most patients ranges of values of bone turnover markers were similar to those in the controls. During our observation, all tested children had normal serum concentration of vitamin D as well as of calcium and phosphorus. CONCLUSIONS: Our data show normal bone resorption and formation processes in most patients with celiac disease on gluten-free diet. However, some cases had changes in the pattern of bone turnover markers. Further studies of these patients are needed to assess their predisposition to osteopenia and osteoporosis.

Adolescent↗
PubMed1993

Lymphoproliferative disease of "LAK cell" precursor large granular lymphocytes in association with celiac disease.

We have investigated a case of lymphoproliferative disease of large granular lymphocytes (LDGL) occurring in association with celiac disease, anemia, neutropenia, and carcinomas of the endometrium, breast, and skin. The large granular lymphocyte (LGL) proliferation was monoclonal, T cell in origin, with T cell receptor beta-chain gene rearrangement, and a CD3+, CD8+, CD16+/- phenotype. In spite of the high frequency of LGL, natural killer (NK) cell activity was absent. Stimulation with interleukin-2 in vitro, however, resulted in high lymphokine-activated killer (LAK) cell activity against NK-resistant targets. The T-cell nature of the LAK precursor cells is in contrast to the majority seen in normal peripheral blood. Therapeutic trials of cyclosporin A, low-dose cyclophosphamide, and levamisole were unsuccessful in reducing transfusion requirements. This case is unique in the association of LDGL with celiac disease. It is also unique in that the patient had been followed for several years prior to the onset of the LDGL. The case extends the list of lymphoproliferative disorders documented to be associated with celiac disease and, conversely, adds to our knowledge of lymphoproliferative disorder of LGL and its "dysimmune" manifestations.

Celiac Disease↗
PubMed1998

Superior mesenteric artery blood flow in children with celiac disease.

BACKGROUND: Knowledge of splanchinic hemodynamics in celiac disease is scarce. The hemodynamic parameters of the superior mesenteric artery were evaluated by duplex Doppler ultrasonography in children with celiac disease to show whether histomorphologic changes in small bowel mucosa led to any alteration in splanchinic blood flow. METHODS: The hemodynamic parameters of the superior mesenteric artery were evaluated by Doppler ultrasonography in 23 children with celiac disease. Ten patients were studied at the time of diagnosis. The remaining 13 children were studied after complete clinical and histologic recovery induced by gluten-free diet. Additionally, 9 patients out of 13 who were on a gluten-free diet for about 2 years were given gluten challenge, and superior mesenteric artery blood flow was measured after the challenge. The results were compared with those of healthy children. RESULTS: Peak systolic velocity of the superior mesenteric artery was higher in untreated celiac patients than in healthy controls and treated celiac patients. Peak systolic velocity of the superior mesenteric artery in the treated group of children was close to that of control subjects, implying that successful treatment with gluten-free diet improves hemodynamic changes. The comparison of Doppler ultrasonographic measurements of the challenge group before and after the gluten challenge revealed that the peak systolic velocity, resistive index, and blood flow of the superior mesenteric artery were changed significantly. CONCLUSIONS: The pathophysiologic events in small bowel mucosa during the active phase of celiac disease induce some hemodynamic changes that can be detected noninvasively by duplex Doppler ultrasonography.

Biopsy↗
PubMed1997

Screening patients with celiac disease for primary biliary cirrhosis and vice versa.

BACKGROUND: An association between celiac disease and primary biliary cirrhosis has been reported in a few cases, mainly as individual case reports. OBJECTIVES: To screen adult patients with celiac disease for primary biliary cirrhosis and patients with primary biliary cirrhosis for intestinal celiac involvement. METHODS: The celiac group consisted of 336 adults (218 women and 118 men; mean age, 36 yr; range 18-74 yr) with celiac disease diagnosed by serological and histological tests, 38 with newly diagnosed celiac disease and 298 with previously diagnosed celiac disease who were consuming a gluten-free diet. The mean follow-up period was 6 yr (range, 1-16 yr). Liver function parameters and autoantibody levels were determined, and, when indicated, histological tests were performed. The biliary cirrhosis group consisted of 65 subjects (58 women and seven men) (mean age, 59 yr; range, 35-67 yr) with primary biliary cirrhosis diagnosed 1-17 years previously (mean, 7 yr) on the basis of the usual biochemical, serological, and histological criteria. Antigliadin and antiendomysium antibody levels were determined, and two biopsy specimens from the distal duodenum obtained during endoscopy were evaluated. RESULTS: In patients with celiac disease, impairment of liver function was frequently found at diagnosis (16 of 38, or 44%), but primary biliary cirrhosis was diagnosed in only one case. In patients with primary biliary cirrhosis, no cases of celiac disease, as currently defined, were found. CONCLUSIONS: Our findings indicate that celiac disease and primary biliary cirrhosis are rarely associated and support the hypothesis that the intestinal lesions per se are not responsible for the liver disease.

Adolescent↗
PubMed1984

Lymphadenopathy in celiac disease: computed tomographic observations.

Lymphadenopathy in patients with celiac disease is generally viewed with alarm due to the association between celiac disease and intestinal lymphoma. Four patients with celiac disease are described in whom significant mesenteric and paraaortic adenopathy was demonstrated by computed tomography (CT). The subsequent clinical course of these patients revealed no evidence of lymphoma. In two patients with longstanding celiac disease and recent relapse, exploratory laparotomy revealed reactive hyperplasia in the enlarged glands; in one patient this was associated with intestinal ulceration, and in the other no underlying pathology was found. Follow-up CT scans in both these patients demonstrated regression of the findings with clinical improvement. In the other two patients, CT was performed as part of the initial evaluation. Follow-up CT in one of these patients revealed almost complete regression of the adenopathy after institution of a gluten-free diet. The other, with a 2 year duration of CT-documented abdominal adenopathy prior to diagnosis, became asymptomatic with weight gain for over 1 year after institution of a gluten-free diet.

Adult↗
PubMed2001

Quebecers with celiac disease: analysis of dietary problems.

The only known treatment for celiac disease is lifelong avoidance of dietary gluten. For many sufferers from celiac disease, this may be difficult to achieve. The purpose of this study was to analyse dietary habits and related problems of adults afflicted with celiac disease. A questionnaire was mailed to 617 current and former members of the Quebec Celiac Foundation to document health, dietary habits, sources of celiac disease treatment information, daily concerns, and level of difficulty in complying with a gluten-free diet. The final sample size was 234 (75% female). Results indicated that over 35% of participants experienced intestinal discomfort at least twice a week. In addition, 66% felt that their consumption of grain products was insufficient. Only 44% said they had received from dietitians a large quantity of information about celiac disease treatment, and only 57% had a high level of confidence in the information received from dietitians. Thirty-six percent reported difficulty in complying with the gluten-free diet. According to a probit analysis, larger region of residence (p<0.02) and concern about preparing meals (p<0.005) were directly related to difficulty in complying, while older age (p<0.05), satisfaction with gluten-free products (p<0.01), and a high level of confidence in treatment information from gastroenterologists and dietitians (p<0.005) were inversely associated with compliance difficulty. Awareness of these results should encourage dietitians to improve their skills in treating celiac disease.

Adolescent↗
PubMedDate not supplied

Postbulbar duodenal ulceration and stenosis associated with celiac disease.

The case histories of five patients with celiac disease and postbulbar duodenal ulceration and stenosis are presented. Celiac disease was unexpected in three of the five patients until endoscopic biopsy revealed villous atrophy. Our findings suggest that duodenal ulceration and stenosis may be a more common complication of celiac disease than previously thought and may precede the clinical diagnosis of celiac disease or occur when there are minimal symptoms and nonspecific radiographic findings for the disease.

Adult↗
PubMed2001

High prevalence of celiac disease in Italian general population.

The worldwide increase of celiac disease prompted us to assess its prevalence in the Italian general population. The 3483 inhabitants of Campogalliano were tested for immunoglobulin A anti-endomysial antibodies. Twenty subjects showed antibody positivity and duodenal biopsy detected typical mucosal lesions of celiac disease in 17 of them; the remaining three cases had a normal villous architecture, but the finding of increased gamma/delta intraepithelial lymphocytes in all and the heterodimer DQA1*0501, DQB1*0201 in two of them was consistent with potential celiac disease. Only one patient had an overt malabsorption syndrome, characterized by diarrhea, weight loss, and severe weakness. In eight subjects atypical symptoms of celiac disease, such as dyspepsia and depression, were present, whereas the remaining subjects were silent. Celiac disease was more frequent in younger age groups. Our cross-sectional design study demonstrates that celiac disease prevalence in the Italian general population is 4.9 per 1000 (95% CI 2.8-7.8), increasing up to 5.7 per 1000 (95% CI 3.5-8.8) with the inclusion of potential cases.

Adolescent↗
PubMedDate not supplied

[Catch-up growth and final height in celiac disease].

BACKGROUND: Growth retardation resulting from celiac disease diagnosed in infancy or in early childhood is remediable after introduction of a gluten-free diet. The aim of this study was to evaluate long-term growth, catch-up growth and final height in a group of treated patients with celiac disease. METHODS: The study population consisted of 35 patients (13 M, 22 F) with typical celiac disease. Age at diagnosis was 1.17 (+/- 0.69) years. For each patient, the standard deviation score (SDS) and centile of height at diagnosis, target height and final height were elaborated, and linear regression and correlations between SDS of final height and age at diagnosis, SDS of height at diagnosis and SDS of target height, respectively, were calculated. RESULTS: At diagnosis patients had a general tendency to short stature: mean height was 81.8 cm +/- 22.9 cm (SDS -0.75 +/- 1.61), while target height was 164.3 cm +/- 13.5 cm (SDS -0.14 +/- 1.04) and final height 169.2 cm +/- 7.7 cm (SDS 0.41 +/- 1.04). Linear regression and correlations between SDS of final height and age at diagnosis, SDS of height at diagnosis and SDS of target height, respectively, proved nonsignificant. CONCLUSIONS: Irrespective of age and height at diagnosis, catch-up growth was complete in this group of patients, with satisfactory achievement of final height. Only one patient (age at diagnosis 13 years) failed to reach the target height.

Adult↗
PubMed2005

Should adults be screened for celiac disease? What are the benefits and harms of screening?

The symptoms of celiac disease are diverse, and the disease is often asymptomatic. Without active serologic screening, most cases probably remain undiagnosed. Recent serologic screening assays allow mass screening for the disease. However, there is no evidence as yet to suggest that symptom-free celiac disease patients run an increased risk of small intestinal lymphoma or other complications. The prevention of osteoporosis seems to be the strongest indicator for widespread screening today. Screening asymptomatic individuals for celiac disease may be even harmful. A lifelong gluten-free diet is not easy to maintain, and the subject's quality of life may deteriorate. It is also debatable whether patients found by active screening adhere to a gluten-free diet similarly to symptomatic ones. The cost-effectiveness of population screening is dubious. Serologic screening should be applied in individuals with even subtle symptoms indicative of celiac disease, such as subclinical-isolated iron deficiency. In various autoimmune conditions, the risk of celiac disease is approximately 5% and, in individuals with affected first-degree relatives, 15%. Infertility, neurologic symptoms such as polyneuropathy, ataxia, epilepsy with posterior cerebral calcification, and osteoporosis are conditions in which celiac disease should be kept in mind. Elevated aminotransferases and liver failure can lead to a diagnosis of celiac disease. Evidence today does not support mass screening of celiac disease. Instead, increased alertness should be observed in patients at risk of the condition.

Adult↗
PubMed1990

Adherence to gluten-free diet and serum antigliadin antibodies in celiac disease.

In 134 patients with celiac disease the compliance with a gluten-free diet (GFD) and the presence of antigliadin antibodies (AGA) were evaluated. Compliance with the GFD was good in 71%, moderate in 11% and poor in 18%. High levels of AGA (IgA and IgG) were found in 24.2% of patients with good GFD, in 40% of those with moderate GFD and in 75% of those with poor GFD compliance. Our data suggest that the presence of AGA is correlated with the degree of adherence to the GFD, and that AGA measurement may be of some value in the monitoring of GFD in patients with celiac disease.

Antibodies↗
PubMed2000

Gastric metaplasia: a frequently overlooked feature of duodenal biopsy specimens in untreated celiac disease.

BACKGROUND: Duodenal gastric metaplasia is rarely reported in untreated celiac disease, although it is seen in 60% to 100% of duodenal biopsy specimens in nonceliac patients with histologic duodenitis. The low incidence could represent underreporting, a decreased incidence in pediatric patients generally, or the more distal sampling site that is customary for most biopsy specimens that are obtained to diagnose celiac disease. It could also be a unique feature of the inflammatory reaction that characterizes this disease. The purpose of this study was to examine the incidence of gastric metaplasia in duodenal specimens from children with untreated celiac disease with special reference to patient age and biopsy site. METHOD: Formalin-fixed paraffin-embedded specimens of duodenal mucosa were selected from the pathology department's archival material. Sections were either stained histochemically or by immunochemical methods, according to an antigen-retrieval protocol. Forty-four duodenal specimens from untreated patients with celiac disease (n = 22) and control subjects of similar age with normal histology (n = 22) were examined. Ten of each were obtained during upper endoscopy from the proximal duodenum (proximal site) and 12 of each by Crosby capsule near the ligament of Treitz (distal site). RESULTS: All specimens from patients with celiac disease exhibited marked villous atrophy. None had been noted to have gastric metaplasia during routine examination of sections stained by hematoxylin and eosin. Fifteen (68%) of 22 of the celiac specimens and 2 of 22 (9%) control specimens contained gastric metaplasia, identified as patches of gastric-type cells containing MUC5AC (gastric mucin), pS2 (gastric trefoil factor) and neutral (periodic acid-Schiff-positive) mucin. Five of the seven celiac specimens that had no metaplasia showed increased numbers of goblet cells expressing gastric markers. The incidence of gastric metaplasia was not different for endoscopic (70%) or capsule (67%) specimens. Sixty-eight percent (7/11) of patients aged less than 3 years had gastric metaplasia. CONCLUSION: The presence of gastric metaplasia has been previously underreported in celiac disease specimens. Detection would be improved by the routine use of period acid-Schiff/ alcian blue staining. The incidence of gastric metaplasia in celiac disease is not significantly influenced by biopsy site or age at time of the biopsy.

Age Factors↗
PubMed2000

Celiac disease in Turkish children: presentation of 104 cases.

BACKGROUND: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. In the present study, clinical, laboratory and histologic features of 104 patients with celiac disease were evaluated. METHODS: Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken. RESULTS: The mean (+/- SD) patient age was 5.9 +/- 4.1 years (range 10 months-16 years) and the most common symptom was diarrhea (81.7%) followed by abdominal distention, weight loss, anorexia and failure to thrive. Abdominal distention (60.6%), short stature (45.2%) and iron-deficiency anemia were the most common findings. High serum alanine aminotransferase levels were found in 38.3% of patients and these levels became normal after adoption of a gluten-free diet in all but two patients with cirrhosis. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 76, 94 and 90% of patients, respectively. Biopsy of the small intestine revealed that 95, two and seven patients had type 3, type 2, and type 1 lesions, respectively, according to the Marsh classification. There was no statistically significant difference between patients and control groups with regard to antinuclear antibody, antismooth muscle antibody, anti-DNA and anticardiolipin antibodies (IgG and IgM). CONCLUSIONS: Although classical celiac disease was seen in most patients in the present study, clinical variability of the condition should be kept in mind. In particular, patients with uncommon findings, such as short stature, cryptogenic liver disease and iron-deficiency anemia, should also be screened for celiac disease.

Adolescent↗
PubMed1995

Macrolipasemia and celiac disease.

A case of undiagnosed celiac disease associated with macrolipasemia and macroamylasemia is reported. This association is almost unique. To our knowledge, only one case has been previously diagnosed. Previous case reports about macroamylasemia and celiac disease, as well as macrolipasemia, are briefly discussed.

Amylases↗
PubMed1995

Low incidence of childhood celiac disease in The Netherlands.

The incidence and prevalence of celiac disease vary internationally. We studied the incidence of identified cases of childhood celiac disease in six Dutch provinces that cover 47.9% of the surface area and 67.6% of the total population of The Netherlands. Children with celiac disease aged 0-14 y, diagnosed from January 1975 to January 1991, were traced by 1) contacting all pediatricians in this area, 2) examining the date of the Dutch National Medical Registration, and 3) investigating the membership records of the Dutch Celiac Disease Society. These data were cross-checked by the Dutch Network and National Database of Pathology. Of the 97.9% of pediatricians who answered our inquiry, 46.1% were treating celiac patients. A total of 342 celiac patients were identified. Informed consent that permitted examination of their medical files was given by 97.3% of the parents of the celiac children. The mean crude incidence rate of diagnosed childhood celiac disease, calculated per 1000 live births per year, was 0.18. However, a significant increase in reported incidence was demonstrated from 0.10 in 1976 to 0.32 in 1990. The best estimate, for the years 1985-1990, is 0.22/1000 live births, which is much lower than in most European countries.

Adolescent↗