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Capsule endoscopy findings in celiac disease associated enteropathy-type intestinal T-cell lymphoma.

Capsule endoscopy is a new technology developed to investigate diseases of the small intestine. It has been shown to be superior to current modalities such as small-bowel radiography and enteroscopy. We describe a patient with long-standing celiac disease who presented with abdominal pain, diarrhea, and weight loss, after many years on a gluten-free diet. The symptom complex and results from small-bowel radiography and computerized tomography raised concern about progression to lymphoma, and ultimately a laparoscopy and small-bowel resection were done for diagnosis. A capsule endoscopy was performed to assess the extent of the patient's enteropathy-type intestinal T-cell lymphoma after three cycles of chemotherapy. We report the first use of capsule endoscopy in the setting of celiac disease associated enteropathy-type intestinal T-cell lymphoma. These endoscopic findings are correlated with those from gross and microscopic pathology and barium small-bowel radiography.

Biopsy↗

Tissue transglutaminase antibodies in celiac disease: assessment of a commercial kit.

OBJECTIVE: Tissue transglutaminase was identified as the autoantigen eliciting endomysial antibody. A homemade enzyme-linked immunosorbent assay (ELISA)-based test was recently developed to determine quantitative titers of IgA antitissue transglutaminase antibody. Our objective in this study was to assess the suitability of a newly developed commercial kit for quantitative determination of antibody in patients with untreated celiac disease. MATERIALS: We tested serum samples from 79 untreated celiac patients, 42 healthy blood donors, and 18 patients with nonceliac intestinal disorders evaluated in two different centers. Samples were tested for antitissue transglutaminase, and antiendomysial and antigliadin antibodies in the center where diagnosis was performed. To assess interlaboratory variability of methods, 24 samples randomly selected were blindly tested in both centers. Antitissue transglutaminase antibodies were determined using a commercial kit (INOVA Diagnostics, Inc., San Diego, CA). RESULTS: Untreated celiac patients had significantly higher titers of antitissue transglutaminase than healthy and disease controls (p < 0.00001). According to the cut-off provided by the manufacturers (20 AU/mL), overall sensitivity was 92% (85% for one center and 100% for the other) and specificity was 98% (100% and 95%, respectively). Antiendomysial antibody was 86% sensitive and 100% specific. Discordance between antitissue transglutaminase and antiendomysial antibodies was detected in 13% of patients. Although two antitissue transglutaminase-negative cases had a positive antiendomysial antibody, the inverse situation was found in eight cases. A blind determination of antitissue transglutaminase on the same samples evidenced a good agreement (kappa statistic: 0.66) between both centers when assessment was qualitative (based on the decision of positive or negative). Although correlation of titers for both determinations was highly significant (r: 0.902, p < 0.00001), a very wide interlaboratory variability (median: 50%) was detected when absolute values were considered. CONCLUSIONS: The quantitative determination of antitissue transglutaminase using a commercial kit was highly sensitive and specific for detection of celiac disease. We observed an incomplete overlapping with antiendomysial antibody. The very high variability of values between laboratories still remains to be solved so as to propose the commercial ELISA assay for the screening of celiac disease.

Adolescent↗

IgA nephropathy associated with celiac disease and dermatitis herpetiformis.

IgA nephropathy was found in three patients with celiac disease; two of them also had dermatitis herpetiformis. These observed associations widen the spectrum of the diseases that have been reported to coexist with IgA nephropathy. This study focused on the possible intestinal origin of the glomerulonephritis.

Adult↗

The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases.

OBJECTIVE: The demographic, clinical, and epidemiological features of subclinical/silent celiac disease in Italy were analyzed in a multicenter study carried out with the participation of 42 centers, in the years between 1990 and 1994. METHODS: One thousand twenty-six subclinical/silent patients (644 children and 382 adults, 702 women and 324 men) were considered eligible for the study. RESULTS: The prevalence of the subclinical/silent form increased significantly during the study both in adults (p < 0.001) and in children (p < 0.005), but its prevalence was always lower (p < 0.001) in children than in adults. This increase appears more likely due to a greater diagnostic awareness and to a better use of screening than to a higher number of subclinical/silent cases. Whereas in 1990 a significantly higher proportion (p < 0.001) of subclinical/silent celiac patients was diagnosed in Northern Italy rather than in Southern-Insular Italy, both in adults (46.7% vs 17.2%) and in children (22.0% vs 9.0%), in 1994 such a difference was no longer conspicuous. Both in children and in adults, iron-deficiency anemia appeared to be the most frequent extraintestinal symptom, followed by short stature in children and cutaneous lesions of dermatitis herpetiformis in adults. In 25.9% of the cases another disease was present, with a significantly higher frequency (p < 0.05) in adults (30.1%) than in children (20.7%). Diabetes and atopy appeared to be the most frequently associated conditions both in children and in adults. CONCLUSIONS: This study has provided an analysis of the largest series of subclinical/silent celiac disease reported to date. In Italy, this form is most frequently recognized in adults, and prospective studies will clarify whether the lower frequency observed in children is a real or apparent phenomenon.

Adolescent↗

Pneumatosis cystoides intestinalis as a complication of celiac disease.

Pneumatosis cystoides intestinalis (PCI) is an uncommon but important condition characterized by the presence of gas-filled cysts in the submucosa and subserosa of the gastrointestinal tract. PCI has been associated with several clinical settings. We report a case where PCI developed in a patient with known celiac disease. To our knowledge, this type of coincidence has been described in seven prior cases. Since PCI often results in pneumoperitoneum through rupture of the cysts, it is important to differentiate the benign form of pneumoperitoneum, in which no intervention is indicated, from the life-threatening form with intestinal infarction and/or perforation, in which immediate surgery is mandatory. Differentiating between them can be difficult; this explains the high rate of negative laparotomy, which, in the past, occurred in 27% of cases. By performing diagnostic laparoscopy, we were able to establish the diagnosis of PCI and exclude intestinal perforation or infarction, thus permitting the patient to avoid an unnecessary laparotomy. Although diagnostic laparoscopy is not routinely indicated as a diagnostic tool for the detection of PCI, it proved to be a safe and accurate method to differentiate between the benign form of PCI and the life-threatening form. Whenever this differentiation has to be made, we recommend that diagnostic laparoscopy be performed first rather than primary laparotomy. Herein, the laparoscopic features of PCI are described and the coincidence of PCI with celiac disease is reviewed.

Aged↗

General screening for celiac disease is advisable in children with type 1 diabetes.

The association between celiac disease (CD) and diabetes mellitus type 1 is well known. Only about one-third of all patients with CD are diagnosed in childhood as a result of typical gastrointestinal symptoms or growth retardation. To evaluate the feasibility of CD screening in diabetic children, we tested autoantibodies to tissue transglutaminase (tTGA) in all children with type 1 diabetes from our pediatric department during a 12-month period. In antibody-positive cases, we analyzed the clinical presentation and offered a duodenal biopsy to confirm the diagnosis and grade the severity of the inflammatory process. Of 205 children, 13 (6.3 %) were tTGA-positive. In seven of eight children who agreed to perform a biopsy, CD typical histological signs were detected (Marsh 1: n = 1, Marsh 3: n = 6). In three patients with confirmed disease, symptoms (iron deficiency, recurrent abdominal pain) remained undiscovered up to time of screening (latent form); in four, the disease was asymptomatic (silent form). Since clinical symptoms are mostly mild or absent in spite of severe signs of duodenal inflammation, we recommend tTGA screening in all diabetic children. This strategy may allow the identification of patients in an early stage in respect of prevention of long-term complications.

Adolescent↗

Selectivity of small intestinal exudate in celiac disease and Crohn's disease.

The small intestinal exudates of patients with protein-losing enteropathies produced by celiac disease or proximal jejunal Crohn's disease were compared with controls. The exudates in control subjects were highly selective, whereas those of the celiac and Crohn's disease subjects were relatively nonselective. It is believed that this loss of selectivity is secondary to basement membrane damage. An analogy is drawn with the renal lesion in nephrotic syndrome where basement membrane damage is associated with nonselective proteinuria.

Adult↗

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.

Adolescent↗

Comparative analysis of conventional training and a computer-based interactive training program for celiac disease patients.

Gluten-free diet (GFD) protects against the complications of celiac disease (CD). However, training in the dietetic field is rare in Germany. Thus, CD patients are likely to benefit from a computer-based interactive training program (CBITP) combined with interactive exercises. We compared a CBITP and a conventional training for CD patients regarding increased knowledge, transferability and sustainability. In that context we analyzed whether CD patients are more able to judge the risk of a food or a situation after practicing with the interactive training software. Sixty-four CD patients were included and randomized in two groups. While the first group used the CBITP, the control group received written instructions. Before and after taking part in the training program and 3 weeks later, the participants filled in a questionnaire for celiac knowledge. The results show that both intervention and control groups increased knowledge about CD. However, the intervention group showed significantly better outcome. A CBITP significantly increases knowledge and sustainability as compared to a conventional training for CD patients. CBITPs can enhance patients' training and treatment.

Adult↗

Improved method for serological testing in celiac disease--IgA anti-endomysium antibody test: a comparison between monkey oesophagus and human umbilical cord as substrate in indirect immunofluorescence test.

The IgA anti-endomysium antibody (IgA-EmA) test has been studied using the indirect immunofluorescence (IF) method with human umbilical cord (HUC) as substrate; 247 sera from patients investigated for celiac disease were tested. The results were in accordance with those obtained using monkey oesophagus (MOE) as substrate. IgA-EmA testing using HUC is shown to have similar reproducibility, sensitivity and specificity as MOE. By avoiding both fixation in chloroform and the blocking step, the processing time for this improved method is decreased by almost 1 h, and the results are stable for reading by fluorescence microscopy for at least 24 h. The indirect IF method using HUC as substrate is easy, reliable and inexpensive. We conclude that the IgA-EmA test using HUC as a substrate can be routinely used for celiac disease screening and follow up.

ABO Blood-Group System↗

Adulthood-onset celiac disease is associated with intercellular adhesion molecule-1 (ICAM-1) gene polymorphism.

Celiac disease (CD) is a multifactorial T-cell-mediated autoimmune disease characterized by gluten-triggered villous atrophy and malabsorption. Although human leukocyte antigen (HLA) class II genes are strong susceptibility factors, non-HLA genes likely contribute to most of CD predisposition. The intercellular adhesion molecule-1 (ICAM-1) gene is a good candidate for CD predisposition because its encoded protein acts as an adhesion and costimulatory receptor. Two single-base polymorphisms (G/A in exon 4 encoding G241R, and A/G in exon 6 encoding K469E) were analyzed in 180 French Caucasian CD case patients (110 patients diagnosed before the age of 15 and 70 patients after the age of 18), and 212 French Caucasian healthy controls. The R241 allele frequency was increased in CD case patients compared with controls (14.2% vs. 5.4% respectively, p = 0.000015, odds ratio [OR] for the R241 allele = 2.9, 95% confidence intervals [CI] = 1.7-4.8). After stratifying for age of disease onset, the R241 variant mainly conferred predisposition to CD occurring during adulthood (OR = 4.2, 95% CI = 2.3-7.5, Pc = 0.000004 for adulthood-onset CD vs. R = 2.1, 95%, CI = 1.2-3.9, Pc = 0.0047 for childhood-onset CD). Position 241 of ICAM-1 maps to the binding site for the integrin Mac-1 and might modify the strength of interaction between endothelium and immune cells. If confirmed in independent datasets, these results may be of importance in at-risk individuals to distinguish rapid from delayed progression to clinical CD.

Adolescent↗

Celiac disease and recurrent aphthous stomatitis: a report and review of the literature.

Celiac disease (CD) is a condition related to the small intestine's intolerance to gluten. The diagnosis of CD can be difficult, especially because patients may exhibit a wide spectrum of signs and symptoms. It is important to identify this disease process early because affected individuals have an increased risk for developing lymphoma of the gut. Our objective was to evaluate whether patients with CD have a significantly higher prevalence of recurrent aphthous stomatitis compared with the general population, as some investigators have speculated. Therefore, we screened 61 patients with diagnosed CD for the presence of, or a positive history of, aphthous ulcerations. We then statistically compared this data with a randomly selected control population, matched for age and gender, but without CD. Our results demonstrated no significant differences between groups for age, gender, or prevalence of recurrent aphthous stomatitis.

Adult↗

Dental enamel defects in celiac disease.

The teeth of 40 adults aged 19 to 67 yr with celiac disease (CD) were examined for dental enamel defects (ED). A total of 33 of the 40 adults with CD (83%) had systematic ED in contrast to only 5 of the 112 clinical controls (4%). Unspecific enamel lesions were found in both groups, but they were more common in the control group (80% vs. 18%). Altogether 69% of the permanent teeth in adults with CD were found to be defected, in clinical controls only 19%. In adults with CD the ED were in contrast to those in controls symmetrically and chronologically distributed in all four sections of dentition. The present study clearly shows that symmetrically and chronologically distributed enamel defects are strongly associated with CD. Therefore in the absence of symptoms and signs of malabsorption dentists could easily select the right patients possibly suffering from CD for gastroenterologic consultations.

Adult↗

Immunology of celiac disease: tissue and species specificity of endomysial and reticulin antibodies.

Patients with celiac disease and dermatitis herpetiformis have circulating antibodies to reticulin and endomysium, the 'extracellular matrix' components as defined by their detection on rodent and primate tissues, respectively. Because both types of antibodies occur in both forms of gluten-sensitive enteropathy, studies were conducted to determine if the two types of antibodies can be distinguished by species and organ specificity. The results of these studies indicate that distinct endomysium-specific and reticulin-specific antibodies can be found and that these differ in their species specificity; i.e., endomysium antigen occurs in primate and not in rodent tissues while the reticulin antigen occurs in rodent and not in primate tissues. However, the activity of both endomysium and reticulin antibodies demonstrates similar tissue distribution, in that both react to antigens associated with gastrointestinal smooth muscles, peritubular and periglomerular areas of the kidney, and sinusoidal and periportal areas of the liver. Also, both antigens seem to be present in sheep and goat tissue. These studies indicate that the antigens reactive with endomysial antibodies are distinct from those reactive with reticulin antibodies.

Animals↗

[The catamnesis of children with celiac disease].

A prospective follow-up was conducted of 29 patients with celiac disease 3 to 10 years in duration. Of these, 8 were on a spare agluten diet, in whom the time-related course of clinical manifestations of the illness was characterized by stabilization of the primary symptoms of disturbed intestinal absorption, improvement in the psychoemotional state at year of their prophylactic management. The glucose tolerance test had gotten normalized after two years of being on a spare diet, lactose tolerance test remaining below the normal range in 37.5 percent of cases at year 3 of the observation, with the content of IgG antibodies to gliadine exceeding the threshold values in 33.3% on an average three times as much as the norm. In those patients having not been on a spare diet, retardation in physical development was recordable together with bone abnormalities manifested by pathologic fractures of the tubular bones. The level of anti-gliadine antibodies of both classes was found to be augmented in 71.4 percent of cases, their values having been fifty times as much as the norm. Glucose tolerance test suggested to us a steady decline in the absorption that was still to be seen at year 10 of the prospective follow-up. Lactase intolerance was somewhat less, remaining at lower values in the half of the patient population.

Celiac Disease↗

Celiac disease and HLA in a Bedouin kindred.

We report the prevalence of celiac disease (CD) and its relationship with other autoimmune diseases and HLA haplotypes in a Bedouin kindred. Of 175 individuals sampled and typed for autoantibodies and HLA class II genotypes, six (3.4%) members had CD, and an additional 10 (5.7%) members tested positive for autoantibodies to transglutaminase (TgAA+). Several CD/TgAA+ relatives also had islet cell antigen or adrenal autoimmunity. Affected relatives are more closely related than expected from the pedigree relationships of all family members and were more often the offspring of consanguineous marriages. Individuals with CD or TgAA+ were enriched for DRB1*0301-DQA1*0501-DQB1*0201, a haplotype previously reported as high risk for CD. There was also an increased frequency of DQB1*0201/DQB1*0201 homozygotes among affected relatives. We found no evidence that DRB1*0701-DQA1*0201-DQB1*0201/DRB1*11-DQA1*0501-DQB1*0301 is a high-risk genotype, consistent with other studies of Arab communities. In addition, a nonparametric linkage analysis of 376 autosomal markers revealed suggestive evidence for linkage on chromosome 12p13 at marker D12S364 (NPL = 2.009, p = 0.0098). There were no other significant results, including the HLA region or any other previously reported regions. This could reflect the reduced power of family-based linkage and association analyses in isolated inbred populations.

Arabs↗

Celiac disease in children with diarrhea is more frequent than previously suspected.

BACKGROUND: Celiac disease (CD) may be missed or diagnosed late in children with chronic diarrhea. In this study the authors estimated the frequency of CD among pediatric patients with chronic diarrhea based on serologic and pathologic examinations. METHODS: During a 6-year period, all patients with chronic diarrhea of more than 6 weeks referred to the authors' department were included. For each patient, an asymptomatic control was enrolled from among the patients referred to our clinic for other reasons. Serologic tests for CD including immunoglobulin A endomysial antibody and immunoglobulin A antigliadin antibody were performed in all patients and controls. If positive, duodenal biopsy was performed to confirm the diagnosis. Patients subsequently diagnosed as CD were placed on a gluten-free diet and reevaluated after 6 months. RESULTS: 825 cases of diarrhea and 825 controls were enrolled. CD was diagnosed in 54 (6.5%) of the diarrhea patients and seven (0.8%) of the controls. After 6 months of gluten-free diet, 48 (88.8%) patients had significant improvement in symptoms and of these 41 (76.1%) were totally asymptomatic. Forty-two patients allowed repeat endoscopy after 6 months of gluten-free diet and 40 (95.2%) showed improvement in histologic findings. CONCLUSION: CD is common among patients labeled as chronic diarrhea. In this subgroup, gluten-free diet may lead to a significant improvement in symptoms. Routine testing for CD may be indicated in all patients being evaluated for chronic diarrhea.

Adolescent↗

Celiac disease and hypoparathyroidism: cross-reaction of endomysial antibodies with parathyroid tissue.

Celiac disease (CD) is a gluten-sensitive enteropathy characterized by the presence of serum antibodies to endomysial reticulin and gliadin antigens. CD has been associated with various autoimmune endocrine disorders, such as diabetes. We report a rare case of idiopathic hypoparathyroidism with coexistent CD characterized by the presence of serum autoantibodies. Studies were conducted to determine the specificities of these autoantibodies and to localize the antibody binding sites by indirect immunofluorescence and immunoelectron microscopy. Sera from a patient with idiopathic hypoparathyroidism and CD and from two patients with CD alone were tested by indirect immunofluorescence for autoantibodies to parathyroid and endomysial antigens. The specificities of the antibody reactions were determined by testing the sera before and after absorption with monkey stomach tissue. In addition, immunoelectron microscopic studies were performed to determine the localization of the endomysial antigen. Indirect-immunofluorescence studies on the patient's serum were positive with the parathyroid as well as the endomysial substrate. Similar reactions were also observed with the sera of endomysial antibody-positive patients with CD. Absorption of the sera with monkey stomach powder, which is known to have the endomysial antigen, abolished the antibody activities on both the endomysial substrate and the parathyroid tissue. Immunoelectron microscopic studies showed that endomysial antibody activity was associated with antigens localized on the myocyte plasma membrane and in the intercellular spaces. Thus, reactions of the patient's serum with the parathyroid tissue were due to endomysial antibodies and were not parathyroid specific as in patients with idiopathic hypoparathyroidism who did not have coexistent CD. In conclusion, indirect-immunofluorescence tests on parathyroid tissue detect not only tissue-specific antibodies but also cross-reactive antibodies, and this should be taken into consideration when these tests are performed.

Autoantibodies↗