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PubMed2005

Small intestinal contrast ultrasonography-based scoring system: a promising approach for the diagnosis and follow-up of celiac disease.

BACKGROUND: Small intestinal ultrasonography with anechoic contrast agents (SICUS) has been shown to have a diagnostic accuracy on small bowel morphology similar to X-ray barium follow-through. Although extremely investigated by transabdominal ultrasonography, celiac disease, a common disorder of the small bowel, has been never studied by SICUS. AIM: To asses SICUS characteristics of celiac disease patients. PATIENTS AND METHODS: SICUS was performed using PEG 4000 as contrast agent. Twenty-three patients with celiac disease at the first diagnosis were enrolled and 30 healthy volunteers, matched for sex and age, were selected as control group. Celiac disease diagnosis was based on anti-gluten, anti-endomysium, and anti-transglutaminase positivity as well as jejunal histology. The following seven echographic parameters were considered: liquid endoluminal content before contrast, loop diameter, Kerckring's folds, peristaltic waves, ileal jejunalization, mesenteric lymphoadenomegaly, and Doppler resistance index (RI) of mesenteric superior artery. Statistical analysis was performed by Student's t test for unpaired data; one-way analysis of variance was used to correlate echographic and histologic pictures. RESULTS: Loop diameter, Kerckring's fold number, peristaltic waves, and Doppler RI appeared to be significantly different between celiac disease patients and controls. Additionally, liquid content, ileal jejunalization, and mesenteric lymphoadenomegaly were present only in the celiacs (52.1%, 47.7%, and 95.6%, respectively), but not in controls. Only Doppler RI values significantly correlated with the histologic degree of damage. CONCLUSIONS: SICUS could be a reliable and noninvasive technique to confirm a diagnosis of celiac disease performed using conventional investigations. The possibility of investigating the whole small bowel and the safety of repeating examinations could be useful in the follow-up of celiac patients.

Adult↗
PubMed2006

Clinical value of immunoglobulin A antitransglutaminase assay in the diagnosis of celiac disease.

OBJECTIVES: Our goal was to evaluate the possible correspondence between antitissue transglutaminase of immunoglobulin A class levels and stage of mucosal damage in patients affected by celiac disease. In addition, we assessed clinical use of antitissue transglutaminase values to predict biopsy results. METHODS: One thousand eight hundred eighty-six consecutive patients with symptoms suggestive of celiac disease and 305 healthy controls underwent determination of serum levels of immunoglobulin A and antitissue transglutaminase. An intestinal biopsy was performed in subjects with antitissue transglutaminase levels > or = 4 IU/mL and in subjects with negative antitissue transglutaminase levels but with clinical suspicion of celiac disease. Histologic grading of celiac disease was consistent with the Marsh classification. RESULTS: One hundred eighty-six subjects with positive antitissue transglutaminase levels and 91 patients with negative antitissue transglutaminase levels were submitted to biopsy. In all healthy subjects, antitissue transglutaminase results were negative. Histologic evaluations in patients with positive antitissue transglutaminase levels gave the following results: type 0 in 25 patients, type 1 in 3 patients, type 2 in 4 patients, type 3a in 22 patients, type 3b in 74 patients, and type 3c in 58 patients. None of the patients with negative antitissue transglutaminase levels showed histologic findings suggestive of celiac disease. The mean antitissue transglutaminase values in patients without mucosal atrophy were significantly lower than in patients with mucosal atrophy. Antitissue transglutaminase values > or = 20 IU/mL were found in only 1 patient without mucosal atrophy. CONCLUSIONS: Our study found a strong correspondence between antitissue transglutaminase levels and stage of mucosal injury; antitissue transglutaminase values > 20 IU/mL seemed to be strongly predictive of mucosal atrophy.

Adolescent↗
PubMed2002

[Acute intestinal invagination revealing celiac disease in a 9-month-old infant].

UNLABELLED: In most cases bowel intussusception is idiopathic in children. Indirect causes, such as celiac disease, are rare. CASE REPORT: A nine-month-old girl was admitted for a bowel intussusception diagnosed by ultrasonography, yet not confirmed by barium enema. The girl underwent a thorough check up, due to a loss of weight and denutrition symptoms which evidenced immunoglobulin A anti-gliadin, immunoglobulin G anti-gliadin, immunoglobulin A anti-endomysium and antireticulin positive antibodies. Celiac disease was confirmed by bowel biopsy, which revealed a subtotal villous atrophy. Evolution was favourable under a gluten free diet. COMMENTS: The description of a bowel intussusception associated with celiac disease is common. This observation appears to be the earliest case ever described: the patient was only nine months old. The initial procedure is routine: diagnosis by ultrasonography, therapeutic enema and surgery only in case of failure of medical treatment. Intussusception associated with celiac disease often presents in an atypical way: elementary forms, spontaneously resolvent and recidivious. The knowledge of this clinical set of symptoms leads to an early diagnosis of celiac disease. The gluten free diet prevents the recurrence of intussusception.

Acute Disease↗
PubMed1999

High prevalence of silent celiac disease in preschool children screened with IgA/IgG antiendomysium antibodies.

BACKGROUND: Because of the different sensitivity and specificity of serologic tests, the search for silent celiac disease is usually performed with the combined or sequential use of several tests. Among these, the IgA-class endomysium antibody test has the highest specificity and positive predictive value, but it may overlook IgA-deficient patients. METHODS: To test a new one-step screening approach, serum samples from 427 apparently healthy, 3- to 6-year-old Hungarian children were investigated for IgA-class and IgG-class endomysium antibodies using monkey esophagus and human jejunum as substrates. RESULTS: Five new cases with flat mucosa were identified by strong endomysium antibody positivity and subsequent jejunal biopsy, yielding a celiac disease prevalence of 1:85. An additional child may have latent celiac disease (slight histologic changes at present). Two of the screening-detected celiac patients exhibited only IgG-class endomysium antibodies due to associated IgA-deficiency. Despite the young age of the screened population, antigliadin antibodies were positive in only three of the five celiac patients. CONCLUSIONS: Prevalence of celiac disease in the study population was much higher than expected on the basis of antigliadin antibody-based studies. The screening system used detected celiac cases in which there was IgA-deficiency and those in which there was not and also those negative for antigliadin antibodies. The findings suggest the importance of the primary testing of autoantibodies in future celiac disease screening policies.

Autoantibodies↗
PubMed2000

Gastric emptying of solids is delayed in celiac disease and normalizes after gluten withdrawal.

UNLABELLED: Several gastrointestinal motor abnormalities have been detected in patients with celiac disease, but it is unclear whether they are able to influence the gastric emptying rate. The aim of this work was to evaluate the gastric emptying rate of solids in children with celiac disease before and after a gluten-free diet. Nine children with celiac disease and nine healthy controls (age range 4-16 y) underwent a 13C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (t(lag)) were calculated. After 6 mo of a gluten-free diet, all celiac children underwent a repeat 13C-octanoic acid breath test. The gastric motility parameters, t1/2 and t(lag), were significantly longer in patients than in controls. No significant correlation between abnormal gastric emptying and specific symptom patterns or severity of histological damage was found. On a gluten-free diet, the gastric emptying rate normalized in all celiac patients. This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing the release of neurotransmitters. Alternatively, nutrient malabsorption might determine significant changes in intraluminal milieu, which, in turn, may affect intestinal motor functions. CONCLUSION: patients affected by celiac disease have a markedly delayed gastric emptying of solids, which returns to normal after gluten withdrawal.

Adolescent↗
PubMed2004

Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy.

Our aim was to assess differences in the sensitivities of serologic tests used for the diagnosis of celiac disease among patients with varying degrees of villous atrophy. Among 115 adults with biopsy-proven celiac disease who fulfilled strict criteria, including serologic testing at the time of diagnosis and response to a gluten-free diet, 71% had total villous atrophy and 29% partial villous atrophy. Endomysial antibody was positive in 77% of those with total villous atrophy, compared to 33% with partial villous atrophy (P < 0.001). There was no difference in sensitivity when the type of presentation (classical vs. silent) was compared. Endomysial antibody-positive and negative patients did not differ with respect to age at diagnosis, duration of symptoms, mode of presentation, or family history of celiac disease. All anti-tissue transglutaminase-positive patients had TVA on biopsy. Seronegative celiac disease occurs. Endomysial antibody positivity correlates with more severe villous atrophy and not mode of presentation of celiac disease. Serologic tests, in clinical practice, lack the sensitivity reported in the literature.

Adult↗
PubMed1999

HLA-DR53 molecules are associated with susceptibility to celiac disease and selectively bind gliadin-derived peptides.

Celiac disease (CD) patients usually express a DQ2 heterodimer, whose chains DQalpha1*0501/DQbeta1*0201, are encoded by the genes HLA-DQA1*0501 and DQB1*0201, respectively. Among the DQ2 carriers, the risk of developing disease was shown to correlate with the number of DQbeta1*0201 chains encoded. Studying two separate cohorts of Italian and Tunisian patients, we now show a significant association of celiac disease with expression of either the DQ2 or DR53 heterodimers. The risk is maximal for individuals that carry both DQ2 and DR53 heterodimers. When twenty synthetic peptides overlapping most of A-gliadin sequence were tested for the binding to various purified DR molecules, it was found that DR53 molecules bind selectively and with high affinity (IC50<1 microM) to A-gliadin-derived peptides. These data suggest that both HLA DQ2 and DR53 molecules are associated with increased genetic risk for CD, and provide a possible biochemical basis for this complex association.

Binding, Competitive↗
PubMed1993

[Epidemiologic studies of celiac disease in childhood in the Dresden district].

The incidence and prevalence of celiac disease in children aged 0-16 years during the years 1970-1986 have been studied prospectively in a geographic defined area of Germany. The celiac disease has been diagnosed due to the criteria of ESPGAN. During the mentioned time period, 170 patients with confirmed celiac disease and 399,477 live births were registered. This corresponds to an incidence of 1:2060. In December 1986 384,840 children in the age between 0 and 16 years were living in the region of Dresden. This corresponds to a prevalence of 44/100,000 inhabitants. Girls were more often affected than boys (1.8:1).

Adolescent↗
PubMed1990

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

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

Adolescent↗
PubMed2003

[Prevalence of type 1 diabetes-specific autoantibodies and of certain HLA patterns in celiac disease].

BACKGROUND AND OBJECTIVE: An association between type 1 diabetes mellitus and celiac disease has been known for some time. One in ten type 1 diabetics have immunological markers for celiac disease (CD). But is there, conversely, an increased risk of CD for diabetics? This study was undertaken to answer this question by determining diabetes-associated antibodies and genetic factors in patients with a gluten-sensitive enteropathy (CD). PATIENTS AND METHODS: 68 patients with CD (48 females and 20 males) were investigated by determining the diabetes-associated serological marker GADA (glutamic acid decarboxylase antibodies). 1A-2A (insulinoma-associated protein 2 antibodies), ICA (Islet cell antibodies) and IAA (insulin autoantibodies). Among this cohort were 60 patients up to the age of 25 years and eight adults (average age 41.7 years). In 36 of these patients the HLA was also determined. RESULTS: GADA was found in 6 patients (9%), 1A-2A in eight (12%) and IAA in 21. ICA were not demonstrated in any. Five of the CD patients were positive for several markers. One child, positive for autoantibodies already had manifest diabetes at the time of investigation. None of the patients with autoantibodies had an abnormal glucose metabolism one year later. HLA-DR3, that occurs in both CD and diabetes, was demonstrated in 78% of the patients with CD. The most common constellation, HLA-DR3-DQ2/HLA-DR7-DQ2, was found in 31%. CONCLUSION: This investigation indicates a genetic association between celiac disease and diabetes. Nonetheless, the risk of developing diabetes mellitus is only minimally higher in patients with CD than in the normal population. Therefore, general screening cannot be recommended at present. Further studies will be needed.

Adolescent↗
PubMed2000

[Splenic thrombosis and celiac disease: a fortuitous association?].

BACKGROUND: Rare cases of venous thrombosis associated with celiac disease have been reported. CASE REPORT: We report a case of 40-year-old woman with splenic infarction and splenic venous thrombosis associated with celiac disease. This patient was homozygous for the C677T mutation of the methyltetrahydrofolate reductase (MTHFR) gene and had moderately elevated homocysteinemia. DISCUSSION: We discuss the link between celiac disease and thrombosis as well as the interest and appropriate duration of anticoagulation and hypothesize a mechanism of thrombotic disease in this setting with hyperhomocyseinemia.

Abdominal Pain↗
PubMed2004

Deamidation and cross-linking of gliadin peptides by transglutaminases and the relation to celiac disease.

Activation of small intestinal gluten-reactive CD4+ T cells is a critical event in celiac disease. Such cells predominantly recognise gluten peptides in which specific glutamines are deamidated. Deamidation may be catalysed by intestinal tissue transglutaminase (TG2), a protein which is also the main autoantigen in celiac disease. Our aim was to study how the two main catalytic activities of transglutaminase--deamidation and transamidation (cross-linking) of an immunodominant gliadin epitope--are influenced by the presence of acceptor amines in the intestinal mucosa, and thereby contribute to further elucidation of the pathogenetic mechanisms in celiac disease. We prepared monoclonal antibodies, reacting specifically with the non-deamidated epitope QPFPQPQLPYPQPQ-amide and/or the deamidated epitope QPFPQPELPYPQPQ-amide. A solid phase immunoassay combined with gel filtration chromatography was used to analyse deamidation and cross-linking of these peptides to proteins. Our results show that QPFPQPQLPYPQPQ-amide was deamidated when incubated with purified TG2, with fresh mucosal sheets and with mucosal homogenates. Of other transglutaminases tested, only Streptoverticillium transglutaminase was able to generate the deamidated epitope. A fraction of the non-deamidated epitope was cross-linked to proteins, including TG2. The results suggest that intestinal TG2 is responsible for generation of the active deamidated epitope. As the epitope often occurs in a repeat structure, the result may be cross-linking of a deamidated, i.e., activated cell epitope. Alternatively, the deamidation may occur by reversal of the cross-linking reaction. The results provide a basis for the suggestion that binding of a peptide to a protein, in connection to its modification to a T cell epitope, might be a general explanation for the role of TG2 in celiac disease and a possible mechanism for the generation of autoantigens.

Albumins↗
PubMed2006

Celiac disease occurring in a patient with hypoparathyroidism and autoimmune thyroid disease.

Patients with an underlying autoimmune endocrine disorder are at an increased risk of developing other autoimmune diseases. We describe a patient with idiopathic autoimmune hypoparathyroidism who developed hyperthyroidism due to Graves disease and subsequently was diagnosed with celiac disease. Malabsorption of L-thyroxine was the only clue regarding the presence of celiac disease. This particular association of these three autoimmune disorders occurring in the same patient has not, to our knowledge, been previously reported. The presentation, investigations performed, and treatment provided are discussed and the literature pertaining to similar cases is reviewed.

Adult↗
PubMed1990

Coexistence of celiac disease and Down syndrome.

Three patients with Down syndrome and celiac disease were described. The incidence of celiac disease among patients with Down syndrome was calculated to be 8 per 1,000 live-born cases, a figure 20 times greater than in children without Down syndrome, indicating that it should be kept in mind when examining patients suffering from recurrent diarrhea and/or delayed puberty.

Adolescent↗
PubMed2004

Accuracy of ultrasonography in predicting celiac disease.

BACKGROUND: Various ultrasonographic (US) signs have been reported in overt celiac disease (CD). The aim of this study was to investigate the diagnostic accuracy of 6 US parameters in predicting CD. METHODS: One hundred sixty-two consecutive patients with chronic diarrhea (n=105), iron deficiency anemia (n=25), or dyspepsia (n=32) underwent anti-endomysial IgA antibody determination and duodenal biopsy. Moreover, US evaluation of 6 parameters (ie, fasting gallbladder volume, transverse diameter of small bowel loops, thickness of the small bowel wall, pattern of peristalsis, presence of free abdominal fluid, and diameter of the mesenteric lymph nodes) was done by 2 operators blind to the serological and histological findings. The pretest probability of CD was estimated to be between 5% and 10%. The percentage of agreement between US and histologic findings, the sensitivity, specificity, positive and negative likelihood ratios, and the posttest probability for positive and negative results were calculated. RESULTS: Celiac disease was diagnosed in 12 patients (7.4%). An increased gallbladder volume, the presence of free fluid in the abdominal cavity, and enlarged mesenteric lymph nodes showed a specificity of 96%, 96%, and 97%, respectively (95% confidence intervals [CIs], 92%-99%, 93%-99%, and 95%-99%), whereas the presence of dilated small bowel loops with increased fluid content and increased peristalsis had a sensitivity of 92% and 83%, respectively (95% CIs, 76%-100% and 62%-100%). Eleven (92%) of the 12 patients with celiac disease and 35 (23%) of the 150 patients who did not have the disease had at least 1 US sign (P=.001); all of the US signs were concomitantly present in 4 patients with CD (33%) and 1 patient without CD (0.6%) (P=.001). CONCLUSION: Ultrasonographic evaluation can accurately predict CD but its place in the diagnostic algorithm depends upon the probability of the disease in the considered population.

Adolescent↗
PubMed1997

Celiac disease transmitted by allogeneic non-T cell-depleted bone marrow transplantation.

We observed the occurrence of celiac disease following allogeneic bone marrow transplantation in a patient transplanted for acute leukemia. The marrow donor was his HLA-identical sister, who had suffered from celiac disease since birth. The post-transplant period was characterized by recurrent episodes of diarrhea. Detailed workup showed atrophic intestinal mucosa on histology and anti-gliadin and anti-endomysium antibodies in the serum, features that were not present before transplantation. GVHD was absent at that time. The patient remains free of symptoms on gluten-free diet and slight immunosuppression. This case suggests transmission of celiac disease by bone marrow transplantation and supports the T cell concept in celiac disease.

Acute Disease↗
PubMed1985

Plasma enteroglucagon in the control of childhood celiac disease.

To study whether or not plasma enteroglucagon reflects changes of the small intestinal mucosa during different phases of celiac disease, we studied fasting and postprandial concentrations of plasma enteroglucagon, as well as small intestinal mucosa morphology, in children with celiac disease and in a reference group of children without gastrointestinal disorders. The children with celiac disease were studied before dietary treatment, during gluten-free diet, and during gluten challenge. In untreated celiac children we found high mean basal and postprandial plasma enteroglucagon concentrations compared with the reference group (p less than 0.001). After a gluten-free diet period of 0.2-4.5 years (mean, 1.0 year), when the small intestinal histology was normal or only mildly abnormal, there was a decrease of both mean basal plasma enteroglucagon concentration (from 81 to 17 pmol/L; p less than 0.001) and mean postprandial plasma enteroglucagon concentration (from 129 to 39 pmol/L; p less than 0.001). During a subsequent gluten challenge, which resulted in a mucosal relapse, there was a rise in mean postprandial plasma enteroglucagon concentration (from 39 to 74 pmol/L; p less than 0.005), although there was a substantial overlap in values from treated and challenged patients. These findings suggest that plasma enteroglucagon levels, particularly after a mixed meal, are correlated with the small intestinal mucosal morphology in childhood celiac disease. Determination of plasma enteroglucagon may facilitate the control of the dietary adherence during gluten-free diet and may in some children indicate mucosal relapse during gluten challenge. Thus, the number of control biopsies may be reduced.

Adolescent↗
PubMed2000

[Clinico-laboratory parallels during celiac disease in children].

Forty-five patients with celiac disease and 73 with the celiakia syndrome were observed. The clinical picture was identical and was characterized by disordered intestinal absorption. Depression of T and B lymphocytes was typical of both forms of the disease. High values of antigliadin IgA and IgG correlated with the severity of atrophic processes in the small intestinal mucosa. Intestinal microflora was characterized by a decrease in the main defense flora and growth of hemolytical and lactonegative enterobacteria and Proteus. Hypocholesterolemia was characteristic of congenital and acquired celiakia. Hemoglobin and albumin levels were in direct correlation while growth deficiency and increment of glycemia were in inverse correlation in patients with celiac disease. The celiakia syndrome was characterized by an inverse correlation between the number of defecations and content of full-value E. coli, body weight deficit, and glucose tolerance test.

Celiac Disease↗