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Lymphadenopathy in celiac disease: not always a sign of lymphoma.

A patient with celiac disease and mesenteric adenopathy discovered on computerized scanning of the abdomen is described. Lymphadenopathy resolved more than 6 months after the institution of a gluten-free diet. Adenopathy without evidence of lymphoma may be part of the clinical manifestations of patients with celiac disease. Follow-up with computerized tomography may be an option in patients with low clinical suspicion for lymphoma.

Adult↗

Persistent hypertransaminasemia as the presenting feature of celiac disease.

Asymptomatic persistent hypertransaminasemia unrelated to hepatitis viral infection is a common cause of referral to the hepatologist. Less frequent liver diseases should then be considered, as well as extrahepatic-origin hypertransaminasemia. Celiac disease, although it has repeatedly been reported as a cause of persistent hypertransaminasemia, is often not included in its differential diagnosis in the absence of the classic malabsorption syndrome. We present the cases of four patients sent to a liver unit for evaluation of persistent hypertransaminasemia in whom celiac disease was finally discovered. Our report highlights the importance of including celiac disease in list of conditions potentially responsible for chronic hypertransaminasemia of unknown cause.

Adult↗

Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia?

OBJECTIVE: Decreased bone mineral density is a common finding in untreated celiac disease patients. However, the precise pathophysiology of osteopenia remains incompletely understood. Pathological features of gluten sensitivity are associated with local release of proinflammatory and antiinflammatory cytokines. We investigated the serum levels of IL-1beta, IL-6, and IL-1 receptor antagonist in celiac patients and correlated them with bone density measurements. METHODS: We assessed serum samples of 16 female patients at the time of diagnosis (on an unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At the same time, bone mineral density in the lumbar spine and total skeleton was determined by DEXA. RESULTS: Untreated patients had high serum levels of IL-1beta and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1beta levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary, IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine Z-score and IL-6 levels exhibited a significant inverse correlation (r = -0.61; p < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores). CONCLUSIONS: Our data demonstrate that the inflammatory process observed in active celiac disease is associated with high serum levels of IL-1beta and IL-6 and normal levels of IL-1-RA. Treatment significantly reduces both proinflammatory cytokines and significantly increases the antiinflammatory one. We also suggest that these cytokines might have a role in the osteopenia associated with celiac disease.

Absorptiometry, Photon↗

Anthropometry, metabolic control, and thyroid autoimmunity in type 1 diabetes with celiac disease: A multicenter survey.

OBJECTIVE: To investigate the influence of celiac disease (CD) on growth and metabolic control in a nationwide cohort of children and adolescents with type 1 diabetes (T1D). STUDY DESIGN: We analyzed data from 19,796 pediatric patients with T1D in the German pediatric multicenter DPV-database for occurrence of CD. RESULTS: CD-specific antibodies were present in 1326 patients (6.7%). The diagnosis was confirmed in 127 patients (0.6%) by small-bowel biopsy. Female subjects were significantly more predisposed to have T1D and CD. The CD-affected patients in our cohort were significantly younger at diabetes onset. Furthermore, they had significantly lower height-SDS at onset (-0.49 vs -0.06, P < .05), a difference that increased during the course of the disease (-0.80 vs -0.26 after 9 years of diabetes, P < .05). In addition, body mass index-SDS significantly differed between the groups (0.22 vs 0.47, P < .05). Evidence for thyroid disease was more commonly observed in the T1D with CD group (6.3% vs 2.3%, P < .05). HbA1c values were lower in the patients with T1D and CD. CONCLUSIONS: The CD-positive patients were characterized by earlier onset of diabetes and decreased growth and weight gain. These findings emphasize the clinical relevance of celiac disease in patients with autoimmune diabetes.

Adolescent↗

An attempt of specific desensitising treatment with gliadin in celiac disease.

Gluten-free diet is the current treatment of celiac disease. We decided to verify the occurrence of histological and serological modification and/or clinical manifestations during a gradual and progressive introduction of gliadin in the diet and if it may induce a tolerance to food, as it occurs in allergic patients. We studied the case of a celiac woman with complete clinical and histological remittance after 10 years of gluten free diet. She took increasing daily doses of gliadin, reaching the final dose of 9 g of gliadin (15 g of gluten) in 6 months. Then she started a free dietary regimen. During the 15-month follow-up period esophago-gastro-duodenoscopy showed normal Kerckring folds and villi. Anti-gliadin, anti-endomysium and anti-tissue-transglutaminase antibodies, as well as the haematological and biochemical parameters remained normal. Our results represent a new approach in research concerning celiac disease, and could provide a future line of study for its management.

Adult↗

[Celiac disease: evolution in knowledge since its original centennial description up to the present day].

In the recent past, some celiac disease features have been discussed in literature specially related to genetic susceptibility, pathogenesis, clinical presentation and diagnostic criteria. Immunological abnormalities characteristic of celiac disease, such as circulating antibodies and increased numbers of intra-epithelial lymphocytes containing a high percentage of gamma-delta T cells have been demonstrated. Other pictures of clinical presentation besides the classical one deserve attention namely short stature, iron-resistant anaemia, enamel hypoplasia, constipation, neurological manifestation and osteoporosis, among others. Asymptomatic presentation has been recognized since development of serological markers such as anti-gliadin, anti-reticulin and anti-endomysium antibodies. Up to now, small intestinal biopsy is the only decisive diagnostic approach. A Federal law has recently imposed food manufactures to place labels informing the presence of gluten in industrialized foods in Brazil. Lately there has been an increase in celiac disease patients registered in the Brazilian Celiac Association.

Celiac Disease↗

Screening by anti-endomysium antibody for celiac disease in diabetic children and adolescents in Austria.

BACKGROUND: Unrecognized celiac disease (CD) may be found in a substantial proportion of patients with type I diabetes mellitus. METHODS: A cohort of 403 Austrian children and adolescents with type I diabetes mellitus (210 males and 193 females; age range, 1-22 years) was screened for celiac disease using the IgA anti-endomysium antibody test (EMA) and the immunoglobulin (Ig)G anti-gliadin (AGA-IgG) and IgA anti-gliadin (AGA-IgA) antibody test. RESULTS: Twelve patients' sera (2.98%) yielded positive EMA results and two patients' sera (0.49%) with IgA deficiency had high AGA-IgG values. All but one of these patients underwent intestinal biopsy. Six (1.49%) had clear histologic evidence of CD (flat mucosa), whereas three (0.74%) showed minor histologic changes (increase in intraepithelial lymphocytes) and four (0.99%), including the EMA-negative patients with IgA deficiency, had a normal mucosa. When the cases with silent and potential CD were combined, the overall prevalence in the current cohort was 2.98%. There was no difference in the hemoglobin (Hb)A1c level between antibody-positive and -negative patients, and subsequent gluten-free diet did not change this metabolic parameter. CONCLUSION: The prevalence of clinically unrecognized CD, found by EMA screening, is much higher in Austrian children with diabetes than in a comparable population without diabetes. The prevalence of CD in diabetic children in Austria is distinctly lower, however, than in several other countries.

Adolescent↗

Gastrointestinal peptide profile in children with celiac disease.

In order to investigate if a plasma profile of gastrointestinal peptides reflects changes in jejunal mucosa in celiac disease, we studied basal and postprandial plasma levels of gastrin, secretin, somatostatin, vasoactive intestinal polypeptide (VIP), and neurotensin in children with untreated and treated celiac disease and in a control group of children. Basal and 30-min postprandial secretin concentrations were statistically significantly lower in untreated celiac children compared to both treated celiac (p less than 0.01 and p less than 0.05, respectively) and control children (p less than 0.001). Plasma secretin levels 30 min after a breakfast meal were also statistically significantly lower (p less than 0.001) in treated celiac children with respect to the control group. In both untreated and treated celiac groups, basal and postprandial plasma levels of somatostatin and VIP were statistically significantly decreased (p less than 0.001) compared to control children. Moreover, there was a significant rise in postprandial levels of neurotensin after a breakfast meal in untreated celiac children. On the contrary, there was no rise of neurotensin in healthy children. These findings seem to indicate that determination of plasma profile of gastrointestinal peptides in children with celiac disease may be useful in monitoring the development of this disease and, thus, the number of jejunal biopsies could be decreased.

Celiac Disease↗

[Structure of small intestinal mucosa in children with celiac disease in different stages of the disease].

The structure of jejunal mucosa in 100 children with celiac disease (CD) was studied morphometrically by means of light and electron microscopy. Variable in nature and intensity structural changes observed during the period of CD clinical manifestations and in remission depend mainly upon the adequacy of agladinic diet and its duration: Not only the degree of the villi atrophy, but differences in the mucosa thickness observed in a one-third of the patients should be taken into consideration. The restoration of the jejunal mucosa in children with celiac disease proceeds rather slowly and with different speeds this being connected with both possible noncompliance of the strict agliadin diet and different susceptibility to gliadin. Complete restoration of the mucosa occurred in few patients.

Celiac Disease↗

Features of intestinal T-cell lymphomas in Chinese population without evidence of celiac disease and their close association with Epstein-Barr virus infection.

BACKGROUND: Intestinal T-cell lymphoma (ITCL) is a heterogeneous lymphoid neoplastic group with variable clinical and pathological features. ITCL in oriental countries is different from enteropathy-type intestinal T-cell lymphoma (ETCL) in relation to celiac disease and Epstein-Barr virus (EBV). The objective of this study was to investigate the clinicopathological features, immunophenotype, expression of cytotoxic molecule (TIA-1), T-cell receptor (TCR)-gamma gene rearrangement, and Epstein-Barr virus (EBV) latent infection in primary ITCL without celiac disease in Chinese. METHODS: The clinical data of 42 patients were analyzed, and the patients were followed up. Compared with human reactive lymphoid tissues, in situ hybridization for EBER1/2, polymerase chain reaction for TCR-gamma gene rearrangement, and immunohistochemical staining for immunophenotypes, TIA-1 and EBV latent membrane proteins (LMP-1) were investigated. Survival curves of different clinicopathological features, immuno-phenotypes, expression of LMP1, TCR-gamma gene rearrangement and therapy were analyzed. RESULTS: Three fourths of the patients suffered from ITCL in China were men with a peak age incidence in the 4th decade. Common presenting features included fever and hemotochezia. The prognosis was poor with a median survival of 3.0 months. The lesions were mostly localized in the ileocecum and colon. About 38/42 (90.5%) patients demonstrated pleomorphic medium-sized on large cells. Histological features of celiac disease were rarely seen. All 42 patients with ITCL revealed CD45RO positive. Neoplastic cells partially expressed T-cell differentiated antigens (CD3epsilon, CD4, CD8) and NK cell associated antigen (CD56). The positive frequency of CD3epsilon, CD4, CD8 and CD56 was 28/42 (66.7%), 7/42 (16.7%), 10/42 (23.8%) and 12/42 (28.6%) respectively. Thirty-nine cells (92.9%) expressed TIA-1, but none expressed CD20 and CD68. More than half of the patients (64.3%, 64.3% and 59.5%) revealed TCR-gamma gene rearrangement by three different TCR-gamma primers respectively. EBER1/2 was detected in 41 (97.6%) of the 42 patients. The expression frequency of LMP-1 was 38.1% (16/42). CONCLUSIONS: Primary ITCL without celiac disease in Chinese is a special highly EBV-associated clinicopathological entity. There are few similarities in patients with celiac disease in western countries. A small proportion of primary ITCLs in Chinese and extranodal NK/T-cell lymphoma of nasal type belong to the same spectrum.

Adolescent↗

Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome.

OBJECTIVE: This study was undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome. MATERIAL AND METHODS: Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be either AGA- or EMA-positive were investigated further with intestinal biopsy. RESULTS: None of the 43 patients had known celiac disease at entry into the study; 37% (16/43) were found to have AGA levels above normal, and 16% (7/43) to be EMA-positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy. Villous atrophy was present in all 7 of the EMA-positive patients, whereas the villi were normal in 7 of the 13 AGA-positive patients who underwent biopsy. CONCLUSIONS: EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome.

Adolescent↗

Presentation of pediatric celiac disease in the United States: prominent effect of breastfeeding.

Childhood celiac disease (CD) is considered rare in the United States. Consequently there are few data concerning its clinical presentation. A validated questionnaire was distributed to families of children with CD. One hundred forty-one children with biopsy-proven CD were included in the study. We found significant differences in the clinical spectrum of children based on their infant feeding history. Exclusively breastfed children were significantly less likely to report failure to thrive (69% vs 88%, p<0.05) and short stature (37% vs 62%, p<0.05), and had a higher rate of "atypical'' symptoms (p<0.01). Breastfeeding alters the presentation and contributes to atypical presentations of CD and diagnostic delay. Pediatricians need to be aware of the diverse manifestations of celiac disease to reduce diagnostic delay.

Age Distribution↗

Antigliadin antibodies detected by enzyme-linked immunosorbent assay as a marker of childhood celiac disease.

Using an enzyme-linked immunosorbent assay (ELISA) assay, we studied the sera of 17 patients with celiac disease and 114 control subjects for the levels of IgG and IgA antigliadin antibodies. As a group, the patients with celiac disease had significantly higher levels of antigliadin antibodies of both IgG and IgA classes (p less than or equal to 0.001). However, there was a significant overlap of values, resulting in respective sensitivities and specificities of 88% and 90% for IgG antigliadin antibodies, and 73% and 65% for IgA antigliadin antibodies. The combined use of both IgG and IgA antigliadin antibody levels produced a sensitivity of 86% and a specificity of 90%. A gluten-free diet in celiac patients did not seem to affect these results. We conclude that the antigliadin antibody ELISA assay cannot be used as a definitive diagnostic test for celiac disease. The small-bowel biopsy remains the principal diagnostic method; the ELISA assay should, at best, be considered a screening test for this disease.

Antibodies↗

Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease.

We aimed to study the expression and localization of the molecular components of enterocyte junctions in celiac disease together with the level of tyrosine phosphorylation, a phenomenon known to affect their cellular distribution and function, and to explore the influence of proinflammatory cytokines. Duodenal biopsy specimens from patients with celiac disease and control subjects were used for immunoprecipitation, immunoblotting, and immunolocalization by using antioccludin, anti-zonula occludens (ZO)-1, anti-E-cadherin, anti-beta-catenin, and antiphosphotyrosine antibodies. The same procedures were carried out on filter-grown Caco-2 cells incubated in the absence or presence of interferon g and tumor necrosis factor a. In active celiac disease, the absence of a phosphorylated ZO-1 and the extensive phosphorylation of beta-catenin might be responsible for the absence of membranous localization of occludin and E-cadherin, respectively. The in vitro system showed an influence of the cytokines on the assembly of these complexes that proved the opposite to celiac samples as far as tight junctions were concerned because the presence of a phosphorylated ZO-1 enables occludin to localize in the membrane.

Adherens Junctions↗