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PubMed2001

Endoscopic features of celiac disease in children.

BACKGROUND: Endoscopic abnormalities have been described in adult patients with celiac disease that may suggest the diagnosis, especially when the presentation is atypical. METHODS: The duodenum of 140 children undergoing EGD for various different indications was evaluated macroscopically and histologically. RESULTS: Histology revealed total villous atrophy in 80 patients, 79 of whom had celiac disease. Among these, 100% had a mucosal mosaic pattern in the duodenum (sensitivity 98.7%, specificity 96.7%, positive predictive value 97.5%, negative predictive value 98.3%), 70% had scalloped duodenal folds (sensitivity 68.7%, specificity 98.3%, positive predictive value 98.2%, negative predictive value 70.2%), 15% had visible vasculature, and 6% had reduction of duodenal folds. Sensitivity and specificity of endoscopic findings were not modified by chromoendoscopy. Except for the mosaic pattern, the frequency of endoscopic abnormalities increased with age; reduction of duodenal folds was never seen in children with celiac disease who were less than 5 years of age. CONCLUSIONS: The frequency and diagnostic value of endoscopic abnormalities are different in children with celiac disease compared with adults with this disease. Because indications for endoscopy, such as abdominal pain, dyspepsia, and unexplained anemia, can be manifestations of celiac disease, and villous atrophy may have a patchy distribution, awareness of these endoscopic abnormalities is important in the diagnosis of celiac disease in children.

Adolescent↗
PubMed2006

Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study.

OBJECTIVE: Few studies have assessed the role of specific gastrointestinal infections in celiac disease. We investigated whether increased frequency of rotavirus infection, a common cause of gastrointestinal infection and inflammation, predicts increased risk of celiac disease autoimmunity. METHODS: A cohort of 1,931 children from the Denver metropolitan area who carried celiac disease human leukocyte antigen (HLA) risk alleles were followed from infancy for development of celiac disease autoimmunity, defined as positivity at two or more subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies measured using a radioimmunoassay with human recombinant tTG. Blood samples were obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus antibodies were assayed using an indirect enzyme immunoassay in serial serum samples from each case and two matched controls. Frequency of infections were estimated by the number of increases (> 2 assay coefficient of variation) in rotavirus antibody between clinic visits. RESULTS: Fifty-four cases developed celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent rotavirus infections predicted a higher risk of celiac disease autoimmunity (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI] 0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for > or = 2 infections, rate ratio for trend per increase in number of infections = 1.94, 95% CI 1.04-3.61, p = 0.037). The result was similar after adjustment for gender, ethnic group, maternal education, breast-feeding, day-care attendance, number of siblings, season of birth, and number of HLA DR3-DQ2 haplotypes. CONCLUSIONS: This prospective study provides the first indication that a high frequency of rotavirus infections may increase the risk of celiac disease autoimmunity in childhood in genetically predisposed individuals.

Antibodies, Viral↗
PubMed1997

Gastrointestinal permeability in celiac disease.

BACKGROUND & AIMS: Intestinal permeability is increased in patients with active celiac disease. The measurement of sucrose permeability is proposed as a novel means to detect upper gastrointestinal damage, with potentially greater use than conventional methods. The aim of this study was to evaluate the effectiveness of sucrose in the detection of celiac disease. METHODS: Permeability tests were performed in 27 newly diagnosed patients, at diagnosis, after upper gastrointestinal endoscopies were performed to exclude macroscopic gastric lesions, and after 2 months on a gluten-free diet. Results were compared with those obtained in 30 healthy subjects and 7 patients with chronic diarrhea but no evidence of celiac disease. RESULTS: At diagnosis, 25 of 27 patients had increased urinary excretion of sucrose. Mean sucrose excretion in patients with untreated celiac disease was significantly increased compared with healthy controls and controls with disease. Sucrose excretion decreased significantly after treatment and completely normalized in 60% of patients. The lactulose-mannitol ratio was abnormal in 26 of 27 patients, with a mean value significantly greater than that observed in healthy controls. This ratio also significantly declined after treatment; however, no values returned to the normal range. CONCLUSIONS: Increased sucrose permeability is a sensitive marker for advanced celiac disease. Moreover, it decreases rapidly in response to a gluten-free diet and therefore is potentially useful to follow response to therapy.

Adolescent↗
PubMed2000

Prevalence of celiac disease in collagenous and lymphocytic colitis.

Both collagenous and lymphocytic colitis have been described in patients with celiac disease, suggesting an association between the conditions. Over the past few years, the availability, sensitivity and specificity of serological markers for celiac disease have improved - the most recent advancement being the description of tissue transglutaminase as the major antigen for endomysium antibody. A quantitative ELISA was used to measure titres of immunoglobulin A (IgA) antibody to tissue transglutaminase (tTG) along with an immunofluorescent technique for IgA endomysium antibody (EmA) in 15 patients with lymphocytic colitis and eight with collagenous colitis to determine whether celiac disease latency could be detected. One patient with lymphocytic colitis demonstrated both elevated titres of tTG antibody and positive EmA, and small bowel biopsy confirmed celiac disease. One patient with collagenous colitis had a slightly elevated titre of tTG antibody with a negative EmA, and results of a small bowel biopsy were normal. Three other patients with lymphocytic colitis were already treated for previously diagnosed celiac disease. The prevalence of celiac disease occurring in lymphocytic colitis was found to be 27%, but no cases of celiac disease in association with collagenous colitis were found.

Adult↗
PubMed1998

Further studies of anti-endomysium and anti-gliadin antibodies in patients with suspected celiac disease.

BACKGROUND: The finding of characteristic small intestinal mucosal abnormalities on histologic examination of a biopsy specimen remains the first requirement for the diagnosis of celiac disease. A reliable and noninvasive test would be ideal for the patient's convenience and for reducing health-care costs. The sensitivity and specificity of anti-gliadin antibodies (AGA-immunoglobulin [Ig] G, AGA-IgA) have been variable; anti-endomysium IgA (EmA-IgA) is more helpful. In an earlier study conducted at the authors' institution, celiac disease was present in 19 patients examined from 1992 to 1995. Anti-endomysium titers were higher than normal in all 19 patients (100%). Total villous atrophy was seen in 14 of 17 biopsy specimens (82%) and subtotal atrophy in 3 (18%). The purpose of the current study was to evaluate further the accuracy of EmA-IgA in diagnosing celiac disease. METHODS: One hundred seven patients were screened for celiac disease between March 1996 and July 1997. The level of EmA-IgA was measured in all patients, and AGA-IgG and AGA-IgA were measured in 104 patients. Forty-six patients underwent endoscopic biopsy of the small bowel, with measurement of disaccharidase enzymes in 45 patients. RESULTS: Five of 46 patients had celiac disease (three boys and two girls; mean age, 5.3 years; 2-9.5 years); one also had cystic fibrosis and another had insulin-dependent diabetes mellitus. All five had marked to complete villous atrophy with crypt hyperplasia and increased serum EmA-IgA (100% sensitivity). None of the remaining patients had increased EmA-IgA (100% specificity). Serum levels of AGA-IgG and AGA-IgA were increased in all four celiac disease patients (100% sensitivity), but they were also high in patients without celiac disease (38% and 92% specificity, respectively), which compromises their diagnostic value. None of the patients confirmed to have celiac disease had IgA deficiency. Abnormal disaccharidase enzyme activities were documented in all five celiac disease patients: severe generalized deficiency (n = 2), moderately severe generalized deficiency (n = 2), and alactasia with moderate deficiency of the alpha-glucosidases (n = 1). CONCLUSIONS: This study confirmed the reliability and accuracy of EmA-IgA in the diagnosis of celiac disease. Small bowel biopsy may be unnecessary in EmA-positive patients in whom celiac disease is suspected.

Antibodies↗
PubMedDate not supplied

Characteristics and quality of illness behavior in celiac disease.

The study evaluated the illness behavior of patients with celiac disease and the influence of the disease and its treatment on key personality components and adherence to dietary recommendations. Twenty-nine adult patients with celiac disease and 47 matched healthy comparison subjects participated in the study. More than 70% of the celiac disease group scored in the pathological range on at least one scale of the Illness Behavior Questionnaire. Patients who received the diagnosis in adulthood had a lower score for nonconformism, a greater tendency to pretend to be sociable, and higher levels of psychophysiological reactiveness, relative to the comparison subjects. The results suggest that celiac disease may be associated with changes in personality that may interfere with patients' adaptation to living with a chronic disease.

Adult↗
PubMed2000

[Adult celiac disease: importance of delay to diagnosis].

OBJECTIVE: Adult celiac disease is a genetically determined condition resulting from intolerance to gluten. This familial disease is associated with HLA B8 DR3 and is characterized by cytotoxic T-lymphocyte reaction in the digestive wall leading to a maladsorption syndrome. Adult celiac disease would be an expression of a silent disease already present in childhood. PATIENTS AND METHODS: We conducted a retrospective study in 19 patients. Diagnosis was established in a department of internal medicine in adulthood. We analyzed histological findings and the clinical history and course. RESULTS: The age curve at diagnosis peaked at 22 years and 67 years. Female sex predominated. Average delay to diagnosis was 3.1 years. The patients were admitted for reasons other than digestive disorders in 17 out of 19 cases. Careful history taking did however disclose subtle digestive signs. The principal manifestations were hematological disorders such as chronic anemia, abnormal liver function tests, and poor control of associated diseases. Type 1 diabetes mellitus was the main associated disease (4/19). Patients with prolonged nutritional deficiencies experienced serious situations. CONCLUSION: Adult celiac disease is a clinical variant suggesting the presence of other non-digestive disorders. Specific antibodies should be assayed in patients with even minimal signs of deficiency in order to identify associated diseases. The principal cause of mortality is digestive T-cell lymphoma. A gluten-free diet is essential to control the course of this chronic disease.

Adult↗
PubMed2005

Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study.

BACKGROUND & AIMS: Previous studies have raised concern about reduced fertility and increased adverse pregnancy-related events in women with celiac disease, but none has estimated overall fertility compared with the general female population. METHODS: We compared computerized primary care data for 1521 women with celiac disease with data for 7732 age- and practice-matched women without celiac disease. We estimated population-based rates of fertility and adverse pregnancy outcomes. RESULTS: Crude fertility rates were 48.2 and 47.7 live births per 1000 person-years for women with and without celiac disease, respectively (rate ratio, 1.01; 95% confidence interval, 0.90-1.14). Age-specific fertility rates showed that women with celiac disease had lower fertility when younger but higher fertility when older compared with women without celiac disease. This increase in relative fertility with increasing age held whether women had treated or untreated celiac disease. Risks of cesarean section (odds ratio, 1.33; 95% confidence interval, 1.03-1.70) and miscarriage (rate ratio, 1.31; 95% confidence interval, 1.06-1.61) were moderately higher in women with celiac disease, but risks of assisted birth, breech birth, preeclampsia, postpartum hemorrhage, ectopic pregnancy, stillbirth, and termination were similar. CONCLUSIONS: Overall, women with celiac disease have fertility similar to that of the general female population, but they have their babies at an older age. Although our findings may reflect a disease effect, the age shift in fertility rates and the increase in cesarean section risk is consistent with socioeconomic or educational advantages of women with celiac disease.

Abortion, Spontaneous↗
PubMed1983

Isolated ocular myopathy and celiac disease in childhood.

Neurologic deficits complicating celiac disease are well-described in adults. Here we report a 12-year-old girl in whom isolated ocular myopathy was the presenting feature of biopsy-proven celiac disease; the process was apparently reversed by a gluten-free diet and vitamin supplementation.

Celiac Disease↗
PubMed1983

Factor V deficiency and its reversal with gluten restriction. In a patient with celiac disease.

Hemorrhagic manifestations in patients with celiac disease are uncommon and, when present, are usually due to a deficiency of the vitamin K-dependent clotting factors. A patient with celiac disease was seen with a severe bleeding diathesis associated with deficiencies of factor V. The deficiencies of vitamin K-dependent clotting factors were rapidly reversed with parenteral administration of phytonadione. Factor V levels returned to normal levels only after gluten restriction.

Adult↗
PubMedDate not supplied

Coexistence of celiac disease and ulcerative colitis.

Coexistence of celiac disease and ulcerative colitis has been reported from Western countries. We report two patients, a 30-year old man and a 16-year old boy, who presented initially with features of celiac disease and later developed ulcerative colitis.

Adolescent↗
PubMed2003

Celiac disease: a model autoimmune disease with gene therapy applications.

Gene therapy (GT) is still at the 'experimental' stage and some recent setbacks have cooled the potential use of this therapeutic tool even in life-threatening conditions. However, this therapeutic approach has a potential, which is not limited to disease for which we have not other option. There are increasing evidence that GT will be soon used in diseases that are not life threatening. One group of diseases that can benefit from GT is the autoimmune one. Several experimental animal models have indicated the efficacy (proof of principle) of GT. In the present review, we have addressed the possibility that even extremely benign autoimmune-like diseases such as Celiac Disease (CD) might one day profit from this type of therapy. We further point that in conditions such as CD, where the trigger is well known and the pathogenic cascade is relatively well defined, a situation not common in autoimmunity, we can even have a better situation where to explore and use GT to control disease initiation and progression. Once the risks that are still intrinsic to GT will have been reduced the therapeutic options we outline in the present review might not appear too far from reality.

Animals↗
PubMed2001

Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease.

OBJECTIVE: Endomysial antibodies (EMA) are a well-known hallmark of celiac disease, but some recent studies showed that the prevalence of these antibodies in clinical practice is lower than expected. The aim of our study was to determine the prevalence of antigliadin (AGA) and EMA antibodies on a consecutive series of subclinical/silent celiac patients. METHODS: We studied 115 consecutive patients with subclinical (92 patients) or silent (23 patients) forms of celiac disease. AGA and EMA were screened in all patients. Histopathology of celiac disease was expressed according to the Marsh classification. RESULTS: The overall AGA in subclinical form were positive in 77% (14 of 18) of patients with partial villous atrophy (VA), in 84% (21 of 25) of patients with subtotal VA, and in 90% (27 of 30) of patients with total VA, whereas EMA were positive in 88.88% (16 of 18) of patients with partial VA, in 92% (23 of 25) of patients with subtotal VA, and 96.66% (29 of 30) of patients with total VA. On the other hand, AGA were positive in 0% (zero of two) of patients with Marsh I and in 30% (three of 10) of patients with Marsh II, whereas EMA were positive in 0% (zero of two) of patients with Marsh I and in 40% (four of 10) of patients with Marsh II (Marsh I-IIIa vs Marsh IIIb-c, p = < 0.005 in overall AGA-positive patients and p = < 0.0001 in EMA-positive patients). At the same time the overall AGA in silent form were positive in 60% (three of five) of patients with partial VA, in 66.66% (four of six) of patients with subtotal VA, and in 77.77% (seven of nine) of patients with total VA, whereas EMA were positive in 80% (four of five) of patients with partial VA, in 83.33% (five of six) of patients with subtotal VA, and in 88.88% (eight of nine) of patients with total VA. On the other hand, overall AGA were positive in 0% of patients with both Marsh I (zero of one) and Marsh II (zero of two), as well as EMA were positive in 0% with both Marsh I (zero of one) and Marsh II (zero of two) (Marsh I-IIIa vs Marsh IIIb-c, p = < 0.001 in overall AGA-positive patients and p = < 0.007 in EMA-positive patients). CONCLUSIONS: At this time small bowel biopsy seems to be the only correct procedure to diagnose a case of suspected celiac disease, especially in patients with mild symptoms or suspected for celiac disease, because they belong to high-risk groups.

Adolescent↗
PubMed2006

Interleukin-10 haplotypes in Celiac Disease in the Spanish population.

BACKGROUND: Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. The IL-10 gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population. METHODS: A case-control and a familial study were performed. Positions -1082, -819 and -592 of the IL-10 promoter were typed by TaqMan and allele specific PCR. IL10R and IL10G microsatellites were amplified with labelled primers, and they were subsequently run on an automatic sequencer. In this study 446 patients and 573 controls were included, all of them white Spaniards. Extended haplotypes encompassing microsatellites and SNPs were obtained in families and estimated in controls by the Expectation-Maximization algorithm. RESULTS: No significant associations after Bonferroni correction were observed in the SNPs or any of the microsatellites. Stratification by HLA-DQ2 (DQA1*0501-DQB1*02) status did not alter the results. When extended haplotypes were analyzed, no differences were apparent either. CONCLUSION: The IL-10 polymorphisms studied are not associated with celiac disease. Our data suggest that the IL-10 alteration seen in patients may be more consequence than cause of the disease.

Case-Control Studies↗
PubMed1998

Celiac disease and Turner syndrome.

BACKGROUND: Short stature is one of the features of Turner syndrome and a form of presentation of monosymptomatic celiac disease. METHODS: The recognition of celiac disease in two antiendomysium antibody-positive Turner syndrome girls who did not respond to growth hormone treatment led us to perform as a screening for celiac disease IgA and IgG antigliadin antibodies and antiendomysium antibodies determination in other 35 Turner syndrome patients. Intestinal biopsy was proposed to the antiendomysium antibodies-positive girls; in the former, subtotal villous atrophy was found; in the latter, one parent's consent for intestinal biopsy was not obtained. RESULTS: The prevalence of celiac disease in Turner syndrome patients observed in the present study (8.1 if we consider 3 villous atrophy, 10.8 if we consider 4 antiendomysium antibody-positive) is quite high and seems to indicate that the association of these two disorders could not be coincidental. As to the clinical picture, celiac disease appeared atypical in one case, typical in another one and as a silent form in the third case. Of the 3 cases with villous atrophy on gluten-free diet growth hormone therapy was not effective in two girls, who were older than 16 years, while in the younger patient, detected by the screening, a significant increment of height velocity and height Standard Deviation Score for Chronological Age according to Turner references was observed. CONCLUSIONS: This study suggests that celiac disease can be associated with Turner syndrome and even responsible for a failure of growth hormone therapy. Therefore we propose to perform in Turner syndrome patients antiendomysium antibody determination as a screening followed by intestinal biopsy in positive cases. This would be advisable at least before starting growth hormone treatment.

Adolescent↗
PubMed1994

Celiac disease associated with systemic lupus erythematosus.

Celiac disease in children has been occasionally reported to be associated with various disorders such as arthritis, cutaneous vasculitis and diabetes mellitus. We report on a 12-year-old girl with celiac disease, diagnosed at 1 year of age, who developed systemic lupus erythematosus. This association has not yet been reported in children.

Celiac Disease↗
PubMed2003

Increased prevalence of autoimmune diseases in first-degree relatives of patients with celiac disease.

BACKGROUND: The prevalence of autoimmune disorders is increased in patients with celiac disease (CD), and it is unknown whether their first-degree relatives also have a high risk of autoimmune disorders. METHODS: To assess the prevalence of autoimmune diseases in first-degree relatives of CD patients, the authors looked for autoimmune disorders in 225 first-degree relatives of 66 children with CD (group A) and in 232 first-degree relatives of 68 healthy children (group B). For both groups, serologic screening for CD was performed through antiendomysium (EMA) and tissue transglutaminase autoantibodies (tTGAA). EMA- and tTGAA-positive subjects were offered an intestinal biopsy. The age at onset of autoimmune diseases was also recorded in group A. RESULTS: The prevalence of autoimmune disorders was significantly (P = 0.028) higher in group A (11 of 225, 4.8%) than in group B (2 of 232, 0.86%). In relatives of CD patients, the prevalence increased with age (chi2 for trend, 43.5; P < 0.0001). Serologic screening for CD was only positive in group A (15 of 225 subjects). An intestinal biopsy was performed in 13 of these 15 relatives (2 refused biopsy). Eleven of 13 had flat mucosa, with subclinical or silent forms of CD. The prevalence of autoimmune diseases in the EMA- and tTGAA-positive relatives of CD patients was significantly higher (3 of 15, 20%; P = 0.028; odds ratio, 6.3; 95% CI, 1/0.21-1/0.11, 4.9-7.6) than in those who were EMA and tTGAA negative (8/210, 3.8%). CONCLUSIONS: The first-degree relatives of CD patients have an increased risk of autoimmune diseases, most likely connected with unrecognized subclinical or silent forms of CD.

Adolescent↗
PubMed2001

Vitamin B12 deficiency in untreated celiac disease.

OBJECTIVES: Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B12, deficiency in patients with untreated celiac disease. METHODS: Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women, seven men; median age 48 yr, range 22-77 yr) between September 1997 and February 1999. The full blood count, serum vitamin B12, red blood cell folate, and celiac autoantibodies (IgA antigliadin and IgA antiendomysium antibodies) were measured before and after a median of 4 months (range 2-13 months) of treatment with a gluten-free diet. In vitamin B12-deficient patients, intrinsic factor antibodies and a Schilling test, part 1, were performed. RESULTS: A total of 16 (41%) patients were vitamin B12 deficient (<220 ng/L) and 16 (41%) patients (11 women and live men) were anemic. Concomitant folate deficiency was present in only 5/16 (31%) of the vitamin B12 patients. The Schilling test, performed in 10 of the vitamin B12-deficient patients, showed five low and five normal results. Although only five patients received parenteral vitamin B12, at follow-up the vitamin B12 results had normalized in all patients. Acral paraesthesia at presentation in three vitamin B12-deficient patients resolved after vitamin B12 replacement. CONCLUSIONS: Vitamin B12 deficiency is common in untreated celiac disease, and concentrations should be measured routinely before hematinic replacement. Vitamin B12 concentrations normalize on a gluten-free diet alone, but symptomatic patients may require supplementation.

Adult↗