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PubMed1993

[Mitotic index of intraepithelial lymphocytes in children with celiac disease. Retrospective study].

The mitotic activity of epithelial lymphocytes was determined in 69 jejunal biopsies performed in 23 children with celiac disease. The mitotic index (MI) exceeded 0.2% in 46 biopsies obtained in untreated celiac and during acute gluten challenge. In the 23 biopsies made during the period of gluten restriction the mitotic index fell down under 0.2%. This retrospective study confirm the reproducibility of the method proposed by Marsh. The high mitotic index in the first biopsy may be useful to reduce in the future the multiple biopsies currently necessary for the diagnosing celiac disease.

Celiac Disease↗

PubMed2000

A trial of oats in children with newly diagnosed celiac disease.

OBJECTIVE: To determine whether consumption of oats is safe in children with newly diagnosed celiac disease who are starting a gluten-free diet. STUDY DESIGN: We conducted a self-controlled, open-label, 6-month trial of a commercial oat breakfast cereal product. Primary outcome variables were small bowel histomorphology and anti-tissue transglutaminase IgA antibody titer. RESULTS: The 10 children who completed the study were 6.8 +/- 4.0 (mean +/- SD) years of age and 5 were male. Over 6.6 +/- 0.7 months, they consumed 24 grams of oat cereal per day, or 1.2 +/- 0.9 g/kg/d. Compared with start of study, at completion there was a significant decrease in biopsy score (P <.01), intra-epithelial lymphocyte count (P <.005), anti-tissue transglutaminase IgA antibody titer (P <.01), and number of symptoms (P <.01). CONCLUSIONS: We conclude that consumption of a commercially available oat cereal product for 6 months is safe for children with celiac disease beginning a gluten-free diet. Studies are needed to determine the long-term safety of including oat cereal in the gluten-free diet.

Avena↗

PubMed2007

Fatal encephalitis in a patient with refractory celiac disease presenting with myorhythmia and carpal spasm.

We report the case of a woman with refractory celiac disease who developed abnormal spontaneous movements of the extremities and face consistent with myorhythmia. Investigation led to a diagnosis of encephalitis, confirmed by postmortem examination. The movements were likely caused by nonparaneoplastic encephalitis associated with refractory celiac disease. Etiologic and diagnostic considerations and treatment options are discussed.

Aged↗

PubMed1985

Increased biliary lipid secretion in celiac disease.

Direct measurements of biliary lipid outputs, cholesterol absorption, and fecal steroids were carried out in celiac patients before and during a gluten-free diet to show whether an enhanced flux of cholesterol into the gut (found earlier in these patients) is due to increased biliary output or mucosal secretion of cholesterol, or both. The bile flow rate and the secretion of biliary cholesterol, phospholipids, and bile acids were significantly increased in celiac disease and appeared to be normalized by effective gluten-free diet. A significant amount of cholesterol originated from the intestinal mucosa, but the amount was not consistently increased in the celiac patients. Fractional absorption of cholesterol was low, but due to enhanced biliary secretion the amount of cholesterol absorbed was mostly within the normal limits so that fecal neutral steroids of biliary origin and cholesterol synthesis were markedly increased in celiac disease. Despite high biliary bile acid secretion, fractional absorption of bile acids was enhanced. Thus, the effective ileal conservation of bile acids could have contributed to increased bile acid-dependent secretion of biliary cholesterol. The enhanced biliary and fecal output of cholesterol should ultimately be balanced by augmented cholesterol synthesis, but the closer site of the synthesis and regulatory mechanisms between cholesterol and lipoprotein metabolism need further exploration.

Adult↗

PubMed2006

Abnormal fatty acid pattern in intestinal mucosa of children with celiac disease is not reflected in serum phospholipids.

OBJECTIVE: Celiac disease (CD) is characterized by chronic inflammation of the small intestinal mucosa with disturbed epithelial transport. The fatty acid (FA) composition of intestinal membranes is important for epithelial function, and disturbances may contribute to the pathophysiology of the disease. We aimed to evaluate whether the intestinal mucosal FA status was reflected in serum phospholipids of patients with CD. PATIENTS AND METHODS: Samples were obtained from 7 pediatric patients with active CD showing mucosal atrophy, 6 pediatric patients with CD in remission, and 11 control pediatric patients with morphologically healthy intestinal mucosa. Small intestinal biopsies were obtained using a Watson biopsy capsule under fluoroscopic control. Blood samples were collected on the same morning after an overnight fast. Tissue phospholipids were isolated by high-performance liquid chromatography, and FAs were analyzed by capillary gas-liquid chromatography. RESULTS: Serum phospholipid FA showed marginal differences between the patients with CD and the controls. Significant differences were observed in mucosa with active CD compared with controls. Linoleic acid (18:2n-6) level was decreased, whereas those of its derivatives were elevated, indicating increased transformation of n-6 FA. Mead acid (20:3n-9) level was increased, with an increased ratio of Mead acid to arachidonic acid (20:4n-6) levels, suggesting essential fatty acid deficiency. The n-3 FA levels were not significantly changed. During remission, the FA pattern of the intestinal mucosa was mainly similar to that in controls. CONCLUSIONS: The FA abnormality of intestinal mucosa in patients with active CD was not reflected in serum values. Altered FA content may contribute to the pathophysiology of the disease because FAs are important for enzymes and for the transport and receptor functions of epithelial membranes.

Adolescent↗

PubMed1991

Immunoglobulin heavy-chain allotypes play a role in the clinical history of celiac disease.

We studied the role of the immunoglobulin heavy-chain allotypes in the evolution of celiac disease. Particularly the Gm(fb) phenotype was investigated since this phenotype is able to determine the breadth of immune response against alpha-gliadin antigen. The results show that weight percentiles and intestinal absorption as assessed by xylose test are influenced by Gm(fb) phenotype suggesting that Gm(fb) genes contribute to the determination of clinical aspects and evolution of celiac disease.

Adolescent↗

PubMed1984

Evaluation of a serum IgA-class reticulin antibody test for the detection of childhood celiac disease.

Serum IgA class reticulin antibody (RA) was found in 28 (97%) of 29 children with flat small bowel mucosa, and in low titer in four (2%) of 245 with normal or near normal mucosa on small intestinal biopsy. Thus the sensitivity of the IgA-RA fluorescent antibody test for screening of celiac disease was 97% and the specificity 98%. IgA-RA was superior to IgG-RA for the detection of celiac disease. During follow-up of patients receiving a gluten-free diet, the IgA-RA rapidly decreased and in most cases disappeared within a year, suggesting that the test may be useful for clinical follow-up of celiac disease as well.

Adolescent↗

PubMed1994

Case report: idiopathic hypoparathyroidism co-existing with celiac disease: immunologic studies.

Idiopathic hypoparathyroidism (IH) is often an isolated disorder in adults, but in children it is usually a component of the autoimmune polyendocrinopathy syndrome. The authors describe a patient diagnosed with isolated IH at age 57 and celiac disease at age 64. Testing of patients' serum show antibodies of the immunoglobulin A isotype against endomysium, reticulin, and gliadin antigens, as well as immunoglobulin G against gliadin. The circulating immunoglobulins reacted with bovine parathyroid tissue, specifically smooth muscle of the blood vessels and glandular cells, as detected by indirect immunofluorescence. Testing of celiac disease positive sera showed similar parathyroid reactivity. When the patient was placed on a gluten-free diet, endomysial, reticulin, and gliadin antibodies decreased to undetectable levels, which was parallel with disappearance of the parathyroid immunoreactivity. The gluten-free diet also produced severe hypercalcemia that responded to calcitriol withdrawal, and ultimately required a reduction by half of the original calcitriol dose. It is possible that in this case the same antibody or antibodies may have caused both hypoparathyroidism and celiac disease. We conclude that, as in the case of childhood-onset IH variants, patients with late-onset isolated IH should be monitored for additional endocrine and extra-endocrine autoimmune disorders.

Celiac Disease↗

PubMed1989

Lactulose/mannitol test: an ideal screen for celiac disease.

A lactulose/mannitol (La/Ma) test was compared with a standard cellobiose/mannitol test (Ce/Ma) in 17 patients with newly diagnosed celiac disease and 12 healthy controls. The mean La/Ma test was 0.163 (SEM 0.076) in celiacs and 0.016 (SEM 0.002) in controls. The mean Ce/Ma test was 0.132 (SEM 0.024) in celiacs and 0.014 (SEM 0.002) in controls (p less than 0.001). There is no significant difference between the new La/Ma test and the Ce/Ma test. Eighty-two patients referred to a general gastroenterology clinic with symptoms or signs of celiac disease performed a La/Ma test. A jejunal biopsy was indicated in 44 of these. In this selected group the sensitivity was 89%, specificity 54%, and negative predictive value of 95%. The La/Ma test fulfills the criteria of a screening test; it is sensitive, of low cost, and simple to perform, and it has the advantage of a simple enzyme assay and does not cause diarrhea in patients with hypolactasia. It can, therefore, be used in screening large patient populations.

Adolescent↗

PubMedDate not supplied

[Predictive value of serological tests in the diagnosis of celiac disease].

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for suspected CD. The study included 130 consecutive patients (age range 16-84 years), who underwent intestinal biopsy for suspected CD. They presented with one or more of the following symptoms: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits and constipation. At the time of admission in the study, an intestinal biopsy was performed and a serum sample was taken for immunoglobulin (Ig) G and IgA AGA, IgA EmA, anti-gp-tTG and anti-h-TG determination. Intestinal histology revealed that 15 patients had partial or total villous atrophy. In these patients the diagnosis of CD was confirmed at subsequent follow-up. The remaining 115 patients included in the study had an intestinal histology characterized by a normal villi/crypts ratio and were considered as controls. Serum EmA, anti-gp-tTG, and anti-h-tTG were positive in all the 15 CD subjects, whereas IgG and IgA AGA were positive in 10/15; in the control group, none were positive for serum EmA, but 11/115 (10%) were positive for anti-gp-tTG and 6/115 (5%) were positive for anti-h-tTG. The sensitivity was 100% for EmA, gp-tTG and h-tTG and 66% for IgA and IgG AGA. The specificity was 100% for EmA, 90% for anti-gp-tTG, 95% for anti-h-tTG, 74% for IgG AGA and 87% for IgA AGA. The negative predictive value was 100% for EmA, anti-h-tTG and anti-gp-tTG, 94% for IgG AGA and 95% for IgA AGA. The positive predictive value was 100% for EmA, 71% for anti-h-tTG (p = 0.03 vs EmA) and 58% for anti-gp-tTG (p = 0.003 vs EmA). Most of the patients who were false positive for anti-tTG had Crohn's disease or chronic liver disease. In conclusion, although both the anti-tTG ELISAs evaluated in the present study showed an optimum sensitivity, their low specificity determined positive predictive values which were significantly lower than those of EmA assay. Besides, the positive predictive value of gp-tTG was too low to warrant submitting a patient to intestinal biopsy for suspected CD.

Adolescent↗

PubMed1990

Reassessment of HLA association with celiac disease in special reference to the DP association.

Patients with the late-onset form of celiac disease have been studied for HLA association by conventional serology (DR and DQ typing) and by oligonucleotide probing with gene amplification (DP typing). Patients and controls were sampled in the Bologna area of northern Italy. Almost all patients were positive for DQw2 (94%), being DR3 positive (72%) and/or DR7 positive (65%). The proportion of DR3/7 heterozygotes in the patients was significantly increased over that expected from the Hardy-Weinberg equilibrium. No positive association with DR5 and no significant increase of DR5/7 heterozygotes were observed. Among the DP alleles reported to exhibit an association with celiac disease in other populations, only DPB3 showed a moderate increase of a borderline significance, not attributable to a linkage disequilibrium with DQw2.

Alleles↗

PubMed2004

Celiac disease and inflammatory bowel disease in pregnancy.

An adverse influence on reproductive life and obstetric complications are known to occur in women with celiac disease (clinical and subclinical disease) or inflammatory bowel diseases. Treatment can improve the pregnancy outcome; therefore, it is advisable that a clinical evaluation is performed by a joint team of obstetricians, internists and surgeons. The preconception clinical evaluation of the affected women is useful to focus on the different clinical aspects of the disease and to indicate specific therapeutic strategies. In this study a review of the literature regard to celiac disease and inflammatory bowel disease in pregnancy is presented.

Celiac Disease↗

PubMed1980

Adult celiac disease associated with HLA-DRw3 and -DRw7.

Celiac disease (CD), which occurs in Europe with varying frequency, is known to be associated with HLA-B8 and even more strongly with HLA-Dw3 because of the high linkage disequilibrium between these two antigens. After typing for HLA-A, -B and -DR antigens in adult patients with CD, we can confirm the high prevalence of B8 (72.7%) and of DRw3 (63.7%). However we find that DRw7 is also significantly increased (54.5%); DRw3 and DRw7, taken together, represent 86% of our 22 patients.

Absorption↗

PubMed2004

Celiac disease and glycogenic acanthosis: a new association?

UNLABELLED: A 6-y-old boy and an 8-y-old girl were admitted to our clinic with anaemia and failure to thrive. Laboratory tests revealed iron deficiency anaemia and positive antigliadin antibodies in both of the patients. Slightly raised grey-white plaques were observed on oesophageal mucosa during endoscopical investigation of the patients. While intestinal mucosal samples confirmed diagnosis of celiac disease histologically, histopathological assessment of oesophageal lesions demonstrated glycogenic acanthosis. Since glycogenic acanthosis associated with celiac disease hasn't been reported in the literature previously to our knowledge, case reports of our patients were presented. CONCLUSION: We suggest that glycogenic acanthosis needs to be investigated as a possible new association of celiac disease in greater paediatric series.

Celiac Disease↗

PubMedDate not supplied

Aneurysmal bone cyst of the femur in a child with celiac disease.

A case of aneurysmal bone cyst of the femur in a 2-year-old boy with celiac disease is described. The bone cyst presented with a pathological fracture while the boy was undergoing gluten challenge. The definite diagnosis of celiac disease according to the criteria formulated by the European Society for Paediatric Gastroenterology and Nutrition was established. A hypothetical association between the two disorders is discussed.

Bone Cysts↗

PubMed1999

Chronic unexplained hypertransaminasemia may be caused by occult celiac disease.

In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained hypertransaminasemia in comparison with that in the general population (0.5%), 140 consecutive patients with chronic increases of serum transaminases levels of unknown cause were tested for antigliadin and antiendomysium IgA antibodies. All patients with positive antibody tests were offered upper gastrointestinal endoscopy with distal duodenal biopsy. Thirteen patients (9.3%, 95% confidence interval 5. 0-15.4) had positive antigliadin and antiendomysium antibodies. The prevalence of antibodies was 17% in women and 5.4% in men (8/47 vs. 5/93 respectively; relative risk 3.2, 95% confidence interval 1.1-9. 1). Distal duodenal biopsy performed in all but one of the patients showed mild villous atrophy with increased intraepithelial lymphocytes in three cases, subtotal villous atrophy in six, and total villous atrophy in three. The prevalence of celiac disease in the patient group was significantly higher than that in the general population (P <.001) with a relative risk of 18.6 (95% confidence interval 11.1-31.2). On the basis of the present findings, screening for celiac disease is an important tool in the initial diagnostic work-up of patients with chronic unexplained hypertransaminasemia.

Adult↗

PubMed2003

Fluctuating transglutaminase autoantibodies are related to histologic features of celiac disease.

BACKGROUND & AIMS: Asymptomatic children at risk for celiac disease (CD) and seropositive for immunoglobulin A anti-TG autoantibodies (TGAA) may lack small intestinal mucosal changes characteristic of CD. We have followed a group of children with serial testing for TGAA. METHODS: Subjects were a group of at-risk children comprised of infants expressing HLA-DR3 on newborn screening, those with type 1A diabetes, or a first-degree relative of someone with type 1 diabetes. All children participating in the prospective study for development of CD underwent serial testing for TGAA. Data from clinical evaluation and small intestinal biopsy were compared to the TGAA levels followed over time. RESULTS: In 42 children, serial TGAA determinations while on a gluten-containing diet showed levels fluctuating 10-100-fold over 3-12 months. A TGAA index more than 0.5 had a positive predictive value (PPV) for histologic confirmation of CD of 96% (22/23). A TGAA index above the usual cutoff for positivity (0.05) had a PPV of only 76% (28/37). CONCLUSIONS: In children with TGAA seropositivity, the TGAA level varied over time and a higher titer predicted an abnormal biopsy characteristic of CD. A threshold for biopsy for diagnosis of CD could be set higher for screening-identified cases than for clinically identified cases to decrease the frequency of performing "normal" biopsies.

Autoantibodies↗

PubMed1998

HLA-DQ2-negative celiac disease in Finland and Spain.

Genetic susceptibility to celiac disease (CD) is strongly associated with DQA1*0501 and DQB1*02 (= DQ2). To study whether CD patients without DQ2 share other MHC class II or TNF alleles, we screened DQ2-negative patients in Finland and Spain. Twelve of 84 (14%) Finnish patients and 13 of 189 (6%) Spanish patients were negative for DQ2. We observed that all but two of altogether 25 DQ2-negative patients had the DR4 DQ8 haplotype, or either DQA1*0501 or DQB1*02 alone. Also, all but three were positive for DRB4*01. The only patients without any of these alleles were both positive for DR 13. There was a clear difference between Finland and Spain: Ten (83%) of the 12 Finnish DQ2-negative patients but only five (38%) of the 13 Spanish patients had DRB1*03, DQA1*03, DQB1*0302 (= DQ8) alleles. Of the Spanish patients, eight (62%) had DQB1*02 without DQA1*0501 and three (23%) had DQA1*0501 without DQB1*02. None of the TNF, TAP, or DPB1 alleles was found to be significantly associated with CD. Our results indicate that in addition to the DQ2 heterodimer, the other major risk alleles for CD are DR4 DQ8, and either DQA1*0501 or DQB1*02 alone. Patients without these alleles appear to be very rare, only two (0.7%) were identified in altogether 253 patients tested.

Adolescent↗