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PubMed2000

The natural history of gluten sensitivity: report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives.

OBJECTIVE: Early studies revealed that up to 50% of non-atrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment. METHODS: After a median time of 86 months (range: 42-102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy. RESULTS: At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype. CONCLUSIONS: Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.

Adolescent↗

PubMed1982

Identification and measurement of molecular variants of cholecystokinin in duodenal mucosa and plasma. Diminished concentrations in patients with celiac disease.

The amount and type of cholecystokinin (CCK) in duodenal extracts and plasma of celiac patients and normal subjects was studied by radioimmunoassay and gel filtration. In both groups there were similar patterns of molecular forms in extracts of duodenal biopsies, but concentrations in celiac disease were significantly depressed. In boiling water extracts of duodenal mucosa from both groups a factor with the properties of the COOH-terminal octapeptide of cholecystokinin predominated, but there were also significant amounts of a larger molecular weight form. In acid extracts of mucosa a factor with the properties of the 33 or 39 residue form was identified in amounts that were approximately 25% those of CCK8; there were also similar amounts of an acid-soluble form that had an apparent molecular weight higher than CCK39. Plasma immunoreactive cholecystokinin was studied after concentration by immunoaffinity adsorption and fractionation by gel filtration. In normal subjects fasting CCK-like immunoreactivity was less than 0.8 pmol/liter, and after a light breakfast increased to 2.0 +/- 0.7 (range 1.0 to 4.8) pmol/liter; CCK8-like activity accounted for all the increased immunoreactivity. In five of six celiac patients the concentrations of both fasting and postprandial CCK-like immunoreactivity in plasma were undetectable (less than 0.8 pmol/liter). We conclude that diminished production and release of CCK could account for the impaired pancreatic and gall bladder responses to intraluminal stimuli in celiac disease.

Adult↗

PubMed1992

Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease.

Degrees of eosinophil infiltration and eosinophil degranulation, as evidenced by localization of the eosinophil granule major basic protein (MBP), were compared in patients with eosinophilic gastroenteritis, patients with celiac disease, and healthy controls using a specific indirect immunofluorescence technique for the localization of MBP. Formalin-fixed, paraffin-embedded biopsy specimens from the mucosa of the stomach and small intestine of 11 patients with eosinophilic gastroenteritis, from the small intestine of 4 patients with celiac disease, and from the stomach and/or upper small intestine of 18 healthy asymptomatic volunteers were tested. Degrees of eosinophil infiltration and extracellular deposition of MBP were graded by two blinded observers; each section was given a score from 0 (nil) to 4 (marked). In the small bowel biopsy specimens, both eosinophil infiltration and extracellular MBP deposition scores were significantly greater in patients with eosinophilic gastroenteritis and in patients with celiac disease than in controls. In the gastric biopsy specimens, extracellular MBP deposition scores were significantly increased in patients with eosinophilic gastroenteritis compared with controls even though eosinophil infiltration scores did not differ significantly at this site. The results support the hypothesis that the eosinophil, through toxic cationic proteins such as MBP, plays a role in the pathogenesis of these diseases.

Adolescent↗

PubMed1983

Does breast feeding protect against the development of clinical symptoms of celiac disease in children?

A retrospective approach has been adopted to investigate the frequency and duration of breast feeding and the time of gluten introduction in the diet in 216 celiac children and their healthy siblings of three different centers--Naples, Milan, and Turin. In this matched case-control study, the selected controls were healthy siblings of the cases. Children formula-fed from birth, or breast-fed for less than 30 days, were found to have a relative risk of developing symptoms of celiac disease four times higher than children breast-fed for more than 30 days (p less than 0.0001). To investigate more deeply the effect of the duration of breast feeding as a possible protecting factor, the linear trend for different periods of breast feeding was tested and found to be highly significant (G1: 18.3 with 1 df). Therefore, increased duration of breast feeding is associated with decreased risk of developing celiac symptoms. On the contrary, there was no apparent relationship between early introduction of gluten into the diet and frequency of celiac disease. Our findings are consistent with the hypothesis that a wider diffusion of breast feeding is a factor underlying the recently reported decrease of the incidence of celiac disease in children.

Age Factors↗

PubMedDate not supplied

[Coexistence of cystic fibrosis and celiac disease. Description of a clinical case and review of the literature].

A 14-month-old female infant with chronic diarrhea, recurrent respiratory infections and stunted growth was diagnosed as celiac disease with AGA detection and a positive intestinal biopsy. A gluten-free diet was introduced with a poor response. A sweat test was positive and heterozygosis for mutation of CFTR gene (both F508 and G542X) was found, demonstrating an association in the infant between cystic fibrosis and celiac disease. Fifteen cases of such association have been previously described in literature, but only three have been genetically studied. The co-existence of cystic fibrosis and celiac disease in the same subject has to be considered till now a casual finding, but are also discussed hypothesis of a non-casual linkage, formulated by some authors.

Celiac Disease↗

PubMed1998

Autoantibodies to tissue transglutaminase as predictors of celiac disease.

BACKGROUND & AIMS: Immunoglobulin A (IgA) autoantibodies to endomysium (EMA) are highly specific and sensitive markers for celiac disease. Recently, we identified tissue transglutaminase (tTG) as the major if not sole endomysial autoantigen. METHODS: An enzyme-linked immunosorbent assay (ELISA) was established to measure IgA anti-tTG titers in serum samples from 106 celiac patients with partial or subtotal villous atrophy, 43 celiac patients on a gluten-free diet, and 114 diseased and healthy controls. Results were correlated with clinical and histological data and with EMA titers. RESULTS: In patients with biopsy-proven celiac disease consuming a normal, gluten-containing diet, 98.1% of the serum samples had elevated IgA titers against tTG, whereas 94.7% of the control sera were negative. IgA anti-tTG correlated positively with semiquantitative IgA EMA titers (r = 0.862; P < 0.0001). CONCLUSIONS: An ELISA based on tTG allows diagnosis of celiac disease with a high sensitivity and specificity. IgA anti-tTG and IgA EMA show an excellent correlation, further confirming the enzyme as the celiac disease autoantigen. Because the assay is quantitative, not subjected to interobserver variation, and easy to perform, it will be a useful tool for population screening of a hitherto underdiagnosed disease.

Adolescent↗

PubMedDate not supplied

[Prevalence of celiac disease serological markers in Tunisian type 1 diabetic adults].

OBJECTIVE: to evaluate the prevalence of celiac serological markers; anti-transglutaminase (ATGt), anti-endomysium (AE), anti-gliadin (AGD) and anti-reticulin (AR) antibodies; in type 1 diabetic Tunisian adults. SUBJECTS AND METHODS: 261 type 1 diabetic patients aged from 16 to 60 years were enrolled in this prospective study. IgG and IgA transglutaminase and gliadin were measured with ELISA. IgA AE were tested by indirect immunofluorescence using 2 substrates; monkey oesophagus and human umbilical cord. AR were detected by indirect immunofluorescence on rat liver, kidney and stomach. Sera IgA level was measured by turbidimetry. RESULTS: 83/261 of diabetics were positive for at least one antibody, 5.7% had ATGt-A, 3.4% AE on monkey esophagus, 3.1% AE on umbilical cordon, 18% AGD-A, 19.5% AGD-G and 3.1% AR. There was an excellent concordance between AE and ATGt (r = 0.9). Out of the 261 diabetics, 5 had an IgA deficiency and one of them has IgG AE and ATGt. CONCLUSION: serological markers of celiac disease seem to be frequent in diabetics. Nevertheless, diagnosis must be confirmed by histological studies which allow us to know the real prevalence of celiac disease in diabetic adults.

Adolescent↗

PubMed1982

Follow-up of treated adult celiac disease: clinical and morphological studies.

A follow-up study of 18 patients with celiac disease is reported. Adherence to the diet, blood chemistry and serum amino acid concentration were investigated in all patients. In addition, HLA blood group typing was performed. Ten patients agreed to undergo jejunal biopsy, xylose test and X-ray of the small intestine. The jejunal mucosa showed no complete restitution even in patients on a strict diet and function tests were abnormal, too. In this study HLA typing demonstrated an association with HLA-B8, HLA-DR3, and HLA-DR7. The results of the follow-up study are discussed with special reference to therapeutic aim and definition of therapeutic success of the gluten-free diet. In addition, a case of jejunal adenocarcinoma complicating celiac disease is presented.

Adenocarcinoma↗

PubMed1998

Usefulness of videoduodenoscopy and vital dye staining as indicators of mucosal atrophy of celiac disease: assessment of interobserver agreement.

BACKGROUND: The present study was designed to determine the diagnostic usefulness of videoduodenoscopic inspection alone and the addition of vital dye staining in the detection of celiac disease. We additionally sought to evaluate interobserver agreement for specific duodenoscopic markers of mucosal atrophy. METHODS: One hundred sixty-seven consecutive subjects who underwent duodenoscopy for intestinal biopsy were included in a prospective controlled study. Endoscopic examination was performed by experienced endoscopists according to a set protocol using methylene blue (1%) dye. All procedures were recorded on videotape, but only 20 (10 with atrophy and 10 normal) were used in a blinded, independent, randomized analysis by five reviewers to evaluate interobserver agreement. Endoscopic signs indicative of mucosal atrophy were as follows: reduction in the number or loss of Kerkring's folds, "scalloped" folds, "mosaic pattern," and visualization of the underlying blood vessels. RESULTS: Eighty-seven patients had celiac disease (57 newly diagnosed, 30 when treated). Seven treated patients had nonatrophic mucosa. In 80 patients the final diagnosis excluded celiac disease. Videoendoscopic inspection alone correctly identified 75 of 80 patients with complete mucosal atrophy and 86 of 87 with normal mucosa. False-negative diagnoses occurred in treated celiac patients with mild atrophy. Mosaic pattern (89%) and scalloped folds (86%) were the most useful endoscopic signs. Vital dye staining, as assessed by experienced endoscopists, provided identical results to those obtained by inspection alone. Sensitivity, specificity, and positive and negative predictive values for the presence of one or more than one feature were 94%, 100%, 100%, and 96%, respectively. The agreement (kappa statistics) among observers was excellent for the mosaic pattern (kappa: 0.76 for both the videoendoscopic inspection alone and dye staining) and the scalloped folds (kappa: 0.83 and 0.76, respectively) and was fair (kappa: 0.41 and 0.59, respectively) for the reduction in the number or loss of duodenal folds. CONCLUSION: This study confirms that videoduodenoscopy is useful in the detection of intestinal atrophy. Dye staining produces a better delineation of scalloped folds and mosaic pattern in the atrophic mucosa, but did not provide additional information to the expert endoscopist. Finally, interobserver agreement was excellent for the most prevalent signs.

Adult↗

PubMed1999

Assessment of body composition by bioelectrical impedance in adolescent patients with celiac disease.

OBJECTIVE: Assessment of body composition is of primary importance in the management of celiac adolescents. We aimed to evaluate body composition by dual-energy x-ray absorptiometry and bioelectrical impedance in celiac adolescents on a gluten-free diet to investigate whether impedance may provide an alternative method to assess nutritional status in these patients. METHODS: We studied body composition in 43 adolescents affected by celiac disease on a gluten-free diet for > or = 1 yr and 30 healthy subjects. Fat, fat-free, and bone masses were assessed by dual-energy x-ray absorptiometry. Fat and fat-free masses were also assessed by bioelectrical impedance. All anthropometric measurements were performed according to standard procedures. RESULTS: All patients had a significantly lower body weight, height, fat-free mass, bone mineral density (p < 0.001), and body mass index (p < 0.01) compared with controls. In contrast, parameters predicting fat compartment (sum of skinfolds and fat mass) did not differ from those of controls. No significant difference was found between patients strictly adherent to a gluten-free diet and patients partially compliant. Compared with dual-energy x-ray absorptiometry measurements, bioelectrical impedance showed a high accuracy to estimate fat-free mass (R2 = 0.97) and limited accuracy for fat mass (R2 = 0.75). Furthermore, impedance was more reliable for estimating hydration of soft tissue underlying the fat-free mass changes. CONCLUSIONS: In adolescents with celiac disease, after a mean of 1 yr of gluten-free diet all the parameters assessing body compartments, except fat mass, were affected, compared with healthy controls. Bioelectrical impedance holds promise for routine assessment of body composition changes in celiac adolescents on a gluten-free diet.

Absorptiometry, Photon↗

PubMed1993

Sonographic findings in celiac disease.

In 43 children who had been admitted to our department due to symptoms of malabsorption, sonography of the small bowel was performed before biopsy. Seventeen of the patients were shown to have celiac disease. Twenty-six patients had gastroenteritis, postenteritis syndrome, and enteropathic cow's milk allergy, and one patient had sarcoidosis. At the time of diagnosis, 16 children with celiac disease showed a sonographically abnormal appearance of the small-bowel wall structure. In addition to hyperperistalsis, slight ascites, pericardial fluid, or liver tissue texture changes could be found in some of the patients. Relating the findings of abnormal small-bowel wall structures to the data of the small-bowel biopsy, we found a sensitivity of 94% and a specificity of 88% for sonographic detection of changes related to celiac disease. Our findings indicate that sonographic data can be of great help in exploring children with signs of malabsorption. These data provide a further argument for the decision to perform a biopsy of the small bowel.

Biopsy↗

PubMed1990

Growth acceleration and final height after treatment for delayed diagnosis of celiac disease.

The only presenting clinical feature of diagnosing celiac disease (CD) late may be short stature. At the start of treatment with a gluten-free diet (GFD), celiac children show an accelerated growth rate. The real duration of catch-up growth and influence of diet on the final stature has not yet been defined. In order to evaluate the effect of a GFD on growth parameters, 24 children diagnosed late with CD were studied at our center. During the period of diagnosis, weight, height standard deviation score (HSDS), weight and height velocities (WV and HV), bone age (BA), and pubertal stage were recorded. Predicted height (PH) according to the Tanner method, parental height, and target height (TH) were also evaluated at diagnosis. All patients initially presented because of short stature or retarded growth (100% of patients with height less than 5th percentile). Patients showed an increased HV and WV during the first 3 years on a GFD, with maximum growth velocity occurring during the first year, but the catch-up growth was incomplete over 3 years (mean HSDS +/- SD, -1.77 +/- 0.6). Puberty began in all patients at a normal age. The 12 patients who completed pubertal development reached their target height, whatever the duration of the GFD. The final height (between the 1st and 25th percentile) seemed influenced mainly by familial characteristics; height was below the 3rd percentile in 31% of parents examined.

Adolescent↗

PubMedDate not supplied

[Celiac disease: report of 20 cases in Rio Grande do Norte, Brazil].

This paper shows that celiac disease exists in Northeast of Brazil and can be one of the causes of malnutrition in the State of Rio Grande do Norte. The authors present a study of 20 cases of celiac disease in the State of Rio Grande do Norte where there had not been any cases diagnosed before 1978. Ethnic aspects in the State seem to have influenced the occurrence of the disease since the European miscigenation has been more frequent than that of negroes and local indians. The cases are analysed in this paper and correlated with the literature.

Body Height↗

PubMed1993

[New cases of celiac disease detected by anti-endomysial antibody test in families of gluten-sensitive patients and among children examined for non-specific gastrointestinal complaints].

Among 228 relatives of 101 gluten-sensitive patients, 13 anti-endomysium antibody (EmA) positive persons (7 children and 6 adults) were identified. In 12/13 cases jejunal biopsy confirmed severe villous atrophy consistent with celiac disease. In the single EmA positive sibling without villous atrophy the histology is thought to be influenced by a steroid treatment because of pulmonary disease. By routine EmA-testing 12 unexpected EmA positive patients were found out of 756 children with complaints and laboratory results otherwise not justifying jejunal biopsy at the first evaluation. Their initial diagnoses were: proteinuria, colitis, Crohn's disease, rickets, recurrent vomiting, resolved postinfectious lactase deficiency, "previously excluded" celiac disease. Severe villous atrophy could be demonstrated in all EmA positive patients subsequently. In further 204 EmA negative children the biopsy showed no atrophy. EmA positivity may reveal clinically not apparent severe villous atrophy emphasizing the role of a new non invasive and highly specific serological screening method for celiac disease.

Adolescent↗

PubMed2004

Lymphocytic gastritis in pediatric celiac disease -- immunohistochemical study of the intraepithelial lymphocytic component.

BACKGROUND: Lymphocytic gastritis (LG) is defined by the recognition of >25 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells. Approximately 50% of children with celiac disease (CD) present LG, which mainly involves the gastric antrum and disappears after a gluten-free diet. This intraepithelial population of lymphocytes has not been immunophenotypically characterized for this age group. MATERIAL/METHODS: We immunohistochemically analyzed 5 formalin-fixed, paraffin embedded biopsies of LG in children with untreated celiac disease using a panel of antibodies. All patients were diagnosed on the bases of clinical, laboratory and histopathological data. RESULTS: All showed similar results. IEL proved to be CD45RO, CD3, CD7, CD8, and Tia-1 positive, while CD4, CD20, CD79a, CD56, CD57, granzyme B, perforin, TCR gamma-delta, TCR beta (V-19), CD95 (FAS), CD95-L (FAS-L) and HLA II were negative. Many IEL were in apoptosis. CD45RO, CD3 and CD7 presented as membranous staining, while Tia-1 resulted in intracytoplasmic granular brown dots. In 3 cases there were rare lymphocytes with granzyme B-positive granules localized to the lamina propria. None presented Helicobacter pylori -like organisms at the luminal surface. CONCLUSIONS: LG associated with CD in children contains a peculiar CD8+ intraepithelial T-lymphocyte population which immunohistochemically lacks perforin and granzyme B, undergoes apoptosis, and is not associated with substantial damage to the epithelial cells. Our results fit with those reported in adults except for the negative results for granzyme B. The findings appear disparate from the ones described in the duodeno-jejunal mucosa in untreated celiac disease.

Adolescent↗

PubMed1997

Anti-gliadin antibodies in patients with celiac disease cross-react with enterocytes and human calreticulin.

One of the characteristic features of celiac disease is an increase in anti-gliadin antibodies (Abs). Recently we found that some of the monoclonal Abs to gliadin cross-react with molecules on rat enterocytes. One of these cross-reacting molecules was identified as rat calreticulin. This study shows that the levels of serum IgA Abs to gliadin, rat, and human enterocytes; purified enterocyte antigens; and calreticulin in sera from patients with active disease were significantly higher than in patients on a gluten-free diet and healthy controls (P < 0.001). Anti-gliadin Abs were isolated by affinity chromatography from the sera of six active celiac patients. The reactivity of these anti-gliadin Abs was demonstrated to be significantly higher (P < 0.05) with human enterocytes and human calreticulin than with other antigens tested. Furthermore, using isolated patients' anti-gliadin Abs bound to Sepharose 2B, two main proteins of molecular mass 62 and 66 kDa were purified from a lysate of human enterocytes. The 62-kDa enterocyte antigen was identified as human calreticulin. These findings suggest that anti-gliadin Abs may play a pathogenic role in celiac disease by cross-reacting with enterocytes. Calreticulin in enterocytes may be one of the putative targets for autoimmune reactions.

Adolescent↗

PubMed1993

Endocranial calcifications, infantile celiac disease, and epilepsy.

The authors report on five patients (three female, two male) with multiple brain calcifications, infantile celiac disease, and epilepsy. The clinical, neuroradiological, neurophysiological, EEG and evolutional aspects are assessed. The authors propose that all patients with brain calcifications which cannot be traced to other known pathologies should undergo diagnostic tests for a malabsorption syndrome; analogously, patients affected with infantile celiac disease should undergo EEG, followed by a neuroradiological examination if the EEG pattern is found to be altered.

Adolescent↗

PubMed2005

Epidemiological, clinical and histopathologic characteristics of celiac disease: results of a case-finding population-based program in an Italian community.

OBJECTIVE: Celiac disease (CD) is underdiagnosed mainly because of lack of awareness of its heterogeneous clinical presentation. The Center for Surveillance and Control of Celiac Disease (CCD) was set up in June 2000 in the province of Brescia, Northern Italy (1,016,426) inhabitants to enhance case-finding, to standardize diagnostic criteria and to collect epidemiological data. MATERIAL AND METHODS: The CCD has prompted an educational "celiac awareness program" in the primary-care setting focusing on selective serological screening of high-risk groups, and has reviewed by standardized criteria all diagnoses made in the province since 1984. RESULTS: A total of 1437 CD patients have been identified by the CCD, 508 of them diagnosed after June 2000 during the 3 years of activity of the Center (M:F 2:1). Annual incidence was 0.11/1000 before and increased to 0.17/1000 during CCD activity, and this increase was greater for adult (from 0.07/1000 to 0.12/1000) than for pediatric CD (from 0.04/1000 to 0.05/1000). Mean age at diagnosis also increased from 20.2+/-17.7 years to 27.2+/-19.3 years (p<0.0001) as did the proportion of asymptomatic patients (8% versus 15%) before and during CCD activity. There was a linear trend towards increasing proportions of symptomatic patients with increasing severity of histopathologic lesions (p<0.03). CONCLUSIONS: Our results indicate that educational programs promoting serological screening of CD in high-risk groups are effective for case-finding in large communities, particularly among the adult population, and suggest that primary-care doctors caring for adults should be particularly targeted by "celiac awareness programs".

Adolescent↗