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PubMed2007

A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease.

BACKGROUND: Treatment of celiac disease (CD) is based on the avoidance of gluten-containing food. However, it is not known whether trace amounts of gluten are harmful to treated patients. OBJECTIVE: The objective was to establish the safety threshold of prolonged exposure to trace amounts of gluten (ie, contaminating gluten). DESIGN: This was a multicenter, double-blind, placebo-controlled, randomized trial in 49 adults with biopsy-proven CD who were being treated with a gluten-free diet (GFD) for > or =2 y. The background daily gluten intake was maintained at < 5 mg. After a baseline evaluation (t0), patients were assigned to ingest daily for 90 d a capsule containing 0, 10, or 50 mg gluten. Clinical, serologic, and histologic evaluations of the small intestine were performed at t0 and after the gluten microchallenge (t1). RESULTS: At t0, the median villous height/crypt depth (Vh/Cd) in the small-intestinal mucosa was significantly lower and the intraepithelial lymphocyte (IEL) count (x 100 enterocytes) significantly higher in the CD patients (Vh/Cd: 2.20; 95% CI: 2.11, 2.89; IEL: 27; 95% CI: 23, 34) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 2.50, 3.09; IEL: 22; 95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical relapse. At t(1), the percentage change in Vh/Cd was 9% (95% CI: 3%, 15%) in the placebo group (n = 13), -1% (-18%, 68%) in the 10-mg group (n = 13), and -20% (-22%, -13%) in the 50-mg group (n = 13). No significant differences in the IEL count were found between the 3 groups. CONCLUSIONS: The ingestion of contaminating gluten should be kept lower than 50 mg/d in the treatment of CD.

Adult↗
PubMed2004

Association of MHC class I related gene B (MICB) to celiac disease.

BACKGROUND AND AIMS: Celiac disease (CD) is an enteropathic disorder characterized by strong association with HLA-DQ2. Our aim was to investigate whether MICB, a gene located in the MHC class I region, may contribute to CD susceptibility. PATIENTS AND METHODS: Total of 133 CD patients, previously reported to be associated with MICA-A5.1, and 116 controls were initially analyzed. Twenty-eight additional DQ2-negative CD patients were also studied. MICB was typed by PCR using sequence-specific primers. HLA-B, -DRB1, -DQA1, -DQB1, and MICA were also typed. RESULTS: The allele MICB0106 was strongly associated with CD (pc < 0.000001, odds ratio (OR) = 5.6, 95% confidence interval (CI) = 3.1-10.1) and it was overrepresented in atypical patients compared with typical ones (pc = 0.04, OR = 2.9, CI = 1.4-6.1). MICB0106 was part of DR3-DQ2 haplotype (B8-MICA-A5.1-MICB0106-DR3-DQ2), and consequently a strong linkage disequilibrium between MICB0106 with DQ2 (lambdas = 1) and MICA-A5.1 (lambdas = 0.55) was found. To analyze whether the association of MICB is independent of this haplotype, its association was also studied in DQ2-negative patients (n = 46). DQ8 (28%vs 9%, p = 0.0085, pc = NS) and MICB0104 (52%vs 30%, p = 0.01, pc = NS) were increased in DQ2-negative patients. MICA-A5.1 was significantly increased in atypical patients (p(c)= 0.001, OR = 6.4, CI = 2.2-18.4), and this association was independent of DQ2 and DQ8 (pc = 0.02, OR = 2.6, CI = 1.1-6.1). CONCLUSIONS: The expression of MIC genes on enterocytes under stressful conditions and their function as ligands of intraepithelial gammadelta and CD8 T cells, together with the data presented here suggest a potential role of MIC genes in the pathogenesis of CD.

Adult↗
PubMed2002

Lack of correlation between disease activity and decreased stimulated secretion of IL-10 in lymphocytes from patients with celiac disease.

BACKGROUND: Celiac disease (CD) is commonly believed to be a predominantly Th1 disease. However, the exact balance between the Th1 and Th2 arms, as well as the correlation to clinical parameters, remains unclear. The aim was to assess the Th1/Th2 cytokine profile and its correlation to clinical parameters in active and non-active CD patients. METHODS: Peak, total secretion and secretory pattern of the Th1 cytokines (IFN-gamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and stimulated peripheral blood mononuclear cells (PBMC) from 19 CD patients with active and non-active disease and 20 normal controls. RESULTS: Peak and total secretion of IL-10 were significantly reduced in CD patients compared with normal controls. This was due to a persistently flat secretory pattern of IL-10 over time in CD patients. In addition, IFN-gamma/IL-10 and the IL-2/IL-10 ratios of peak and total secretion were higher in patients than in controls. In contrast, peak, total secretion and secretory pattern of IL-2, IFN-gamma and IL-4 were comparable in patients and controls as well as the IL-2/IL-4 and IFN-gamma/IL-4 ratios. No difference in the cytokine secretion or Th1/Th2 ratio was found between active and non-active patients or between pediatric and adult patients. CONCLUSIONS: These data indicate that the Thl/Th2 balance in CD is shifted towards Th1 cytokines because of a down-regulated IL-10 secretion. The aberrant profile of cytokine secretion of these patients is not associated with clinical parameters and suggests an inherent defect in IL-10 secretion in CD.

Adolescent↗
PubMed2000

[Association of asymptomatic celiac disease and Crohn's disease].

A 24-year-old woman had Crohn's colitis which had been diagnosed in 1997. The patient was given sulfazalazine and responded well. Antiendomysial and antigliadin antibodies were positive. Diagnosis of celiac disease was confirmed by duodenal biopsy showing villous atrophy and an increased number of lymphocytes infiltrating the epithelium. Few cases associating Crohn's disease and celiac disease have been reported. This case illustrates the complexity of the pathogenic mechanisms in these two disease. Our patient required a gluten-free diet although the celiac disease was asymptomatic, basically to avoid the risk of malignancy associated with celiac disease.

Adult↗
PubMed2003

Prevalence of celiac disease in Brazilian children of short stature.

The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody (> or =1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7% (with another 0.9% of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.

Adolescent↗
PubMed2002

Occurrence of celiac disease after onset of type 1 diabetes: a 6-year prospective longitudinal study.

OBJECTIVE: To investigate the prevalence of celiac disease in a large cohort of children and adolescents at the onset of type 1 diabetes and the occurrence of new cases during a 6-year follow-up. METHODS: We prospectively studied, by repeated serologic screening, 274 consecutive patients at the onset of type 1 diabetes (age [mean +/- standard deviation]: 8.28 +/- 4.65 years) for 6 subsequent years. One patient had a diagnosis of celiac disease before the onset of diabetes. The immunoglobulin A-antiendomysium antibody test was selected as the screening test; patients with positive results (++ or +++) or with 2 consecutive weak positive tests (+) were considered appropriate for the jejunal biopsy. RESULTS: At diabetes onset, 15 (5.5%) of 273 patients tested positive with the antiendomysium test; jejunal biopsy was performed in 10, and celiac disease was diagnosed in 9. The prevalence of biopsy-confirmed celiac disease at the manifestation of diabetes was 3.6% (10 of 274 patients). Twelve more patients with a negative antiendomysium antibody test at diabetes onset tested positive during the follow-up within 4 years; 10 of them had biopsies performed, and 7 had celiac disease. Therefore, the overall prevalence of biopsy-confirmed celiac disease in the entire cohort of patients was 6.2%. The age at diabetes onset in patients with and without celiac disease was not different (7.88 +/- 5.69 vs 8.3 +/- 4.58 years). The majority of cases of celiac disease were asymptomatic in their presentation, and no signs of overt malnutrition were documented. CONCLUSIONS: The prevalence of celiac disease in patients with type 1 diabetes is approximately 20 times higher than in the general population. Sixty percent of cases are already present at diabetes onset, mostly undetected, but an additional 40% of patients develop celiac disease a few years after diabetes onset. Extending screening programs for celiac disease after the onset of type 1 diabetes is recommended, even in the absence of clinical symptoms.

Adolescent↗
PubMed2005

Serological testing for celiac disease in women undergoing assisted reproduction techniques.

BACKGROUND: The assertion of a causal relationship between celiac disease and infertility is suggested by several lines of research. Nevertheless, robust evidence has not yet been provided. The present study evaluated, for the first time, the prevalence of celiac disease in women undergoing assisted reproduction techniques (ART). METHODS: Serum samples from 200 Italian women undergoing ART were evaluated for celiac disease by endomisium antibody (EMA) and transglutaminase antibody (t-TGA)-two highly sensitive and specific serological markers. Two hundred women not reporting reproductive problems and having delivered at least one child served as controls. In cases of positive serology, the diagnosis was confirmed by jejunal biopsy. RESULTS: Five (2.5%) women from the study group and two (1.0%) from the control group were found to have celiac disease (P = 0.44). The main indications for ART in women found to have celiac disease were tubal factor in two cases and male infertility in three cases. None of these women reported major gastrointestinal complaints. Extra intestinal signs linked to celiac disease were noted in four out of five patients. CONCLUSION: This study raises the issue of celiac disease screening in ART programmes. Given the available evidence in the literature combined with our observations from this study, the value of serological testing for celiac disease in infertile women remains uncertain. Further studies to address this issue are required.

Adult↗
PubMedDate not supplied

[Celiac disease in the elderly: a case report].

Celiac disease is not a negligible cause of malabsorption in the elderly. Diarrhea, loss of weight and abdominal discomfort are often absent so that celiac disease has indeed a subtle, paucisymptomatic, course in the elderly. More than 50% of the patients have extraintestinal symptoms; only 10-40% have typical complaints pointing to small-intestinal biopsy. Elimination of gluten from diet is the cornerstone of the therapy. A 73-year-old woman with hyporexia, loss of weight, depression, bowel abnormalities and progressive deterioration of her abilities in the instrumental activities of daily living was referred to our department. Antigliadin and antiendomysial antibodies were present. A subsequent small-intestinal biopsy of the second and third portion of duodenum showed subtotal villous atrophy, increase of intra-epithelial lymphocytes as well as hyperplastic glands (type III Marsh score). All these pathological findings were compatible with celiac disease diagnosis so that a gluten-free diet was then initiated.

Aged↗
PubMed2005

Successful treatment of epilepsy and celiac disease with a gluten-free diet.

Celiac disease is a gluten-sensitive enteropathy, which recently has been described in association with epilepsy or other neurologic disturbances. This study describes a case of a 7-year-old female with intractable-to-treatment epilepsy and late-onset celiac disease, who was treated successfully with a gluten-free diet plus antiepileptic therapy. It is important for children with intractable cases of epilepsy and weight loss to undergo screening for celiac disease.

Anticonvulsants↗
PubMed1997

High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus.

OBJECTIVES: Diagnosis of unrecognized celiac disease is potentially important. The prevalence of celiac disease in patients with insulin-dependent diabetes mellitus is uncertain. We report the prevalence of celiac disease in a stratified random sample (n = 101) of adult insulin-dependent diabetic patients (age, 18-59 yr) attending our clinic, and in an age- and sex-matched control group (n = 51). METHODS: Screening was by anti-endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. RESULTS: Celiac disease had not been suspected in any patient at the time of screening. Eight patients tested positive for anti-endomysial antibody, all of whom had a distal duodenal biopsy performed. Five patients had histologic evidence of celiac disease. One patient with negative histology was receiving immunosuppressive therapy for a renal-pancreas transplant. Of the five patients with abnormal histology, two improved on gluten restriction, one was unable to comply, one refused treatment, and one was lost to follow-up. No control subject tested positive for endomysial antibody. CONCLUSIONS: Patients with insulin-dependent diabetes have an increased prevalence of celiac disease. Because most cases are clinically unrecognized, consideration should be given to screening all insulin-dependent diabetes mellitus patients with endomysial antibodies.

Adolescent↗
PubMed2003

Bone mineral density in children with untreated and treated celiac disease.

OBJECTIVES: Osteopenia is a common complication in adults with celiac disease. The effect of a gluten-free diet on bone mineral density is a matter of controversy. The aim of this study was to investigate bone mineral density in children with celiac disease at diagnosis and in patients treated for 1 year. METHODS: Bone mineral density and bone mineral content were measured in 34 children with untreated celiac disease at diagnosis and in 28 patients on a gluten-free diet for 1 year. The results were compared with those of 64 gender- and age-matched healthy control subjects. Serum calcium, phosphate, alkaline phosphatase, 25 -hydroxy vitamin D, and intact parathormone levels were determined in treated and untreated patients. RESULTS: The mean values of bone mineral density and bone mineral content of untreated patients with celiac were significantly lower than the control group (P = 0.006 and P = 0.005, respectively) and treated patients (P = 0.015 and P = 0.011 respectively). Treated patients had mean bone mineral density and bone mineral content values not significantly different from those of healthy control subjects. Minor hypocalcemia was detected in 17.6% of the patients with new diagnoses and 3.6% of the treated patients. Of the untreated patients, 29.4% had high intact parathormone concentrations; in untreated patients, the total was 14.3%. Untreated patients had significantly lower serum calcium and significantly higher intact parathormone levels than did treated patients. The other bone metabolism parameters were similar in the two celiac groups. CONCLUSION: Children with celiac disease are at risk for reduced bone mineral density. A strict gluten-free diet improves bone mineralization, even in 1 year. Early diagnosis and treatment of celiac disease during childhood will protect the patient from osteoporosis.

Absorptiometry, Photon↗
PubMed2002

Clinical presentation of adult celiac disease in Western Saudi Arabia.

OBJECTIVE: To study the clinical presentation of adult celiac disease. METHODS: A retrospective study of adult patients who were diagnosed with celiac disease based on findings of small intestinal biopsy, response to gluten free diet and exclusion of other causes of malabsorption or vitamin deficiency over a period of 5 years from 1998-2002. The study was carried out at the King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. RESULTS: Sixteen patients were diagnosed with celiac disease. Osteomalacia and iron deficiency anemia were common clinical presentations. Diarrhea, malabsorption associated with growth failure was observed in 3 patients with a mean age of 14.5 years. Celiac disease associated with other autoimmune diseases was reported in 6 patients. Insulin-dependent diabetes mellitus in 3 patients, Hashimoto's hypothyroidism in 2 patients and dermatitis herpetiformis in one patient. No malignancy was observed during the follow-up of our patients. There was a good clinical and biochemical response to gluten free diet in 12 cases. CONCLUSION: Osteomalacia and iron deficiency anemia were common clinical presentations of celiac disease. Hence, the presence of either one of them in a female patient should raise the possibility of celiac disease.

Adult↗
PubMedDate not supplied

Celiac disease presenting as iron-deficiency anemia in northern India.

BACKGROUND: Adult celiac disease is infrequent in India. Iron-deficiency anemia as its presenting manifestation is still rarer. METHODS: We investigated patients with refractory iron-deficiency anemia attending the hematology clinic of a tertiary-care hospital for celiac disease. The diagnosis of celiac disease was based on histology, serology and response to treatment. RESULTS: Of 19 patients with refractory iron-deficiency anemia seen from April 1998 to March 2000, 11 were diagnosed to have celiac disease. Four of these had abnormal D-xylose test and 3 had fat malabsorption. All 11 patients responded to gluten-free diet with improvement in hematological parameters. CONCLUSION: Patients with refractory iron-deficiency anemia of unknown cause should be investigated for subclinical celiac disease.

Adult↗
PubMedDate not supplied

[Undiagnosed celiac disease in childhood].

AIMS: This study was designed to assess the proportion of adult patients with celiac disease who had had undiagnosed symptoms during childhood and to determine the consequences of such diagnostic delay. PATIENTS AND METHODS: One hundred eighty-four patients with celiac disease (56 males, 128 females, age range 17-88 years) were classified according to diagnosis and symptoms of celiac disease during childhood. Prevalence of short stature, low fertility, clinical osteoporosis, cancer, and autoimmune disease were assessed in each celiac group and compared with a control group matched for gender and age. RESULTS: Compared with the control group, patients with celiac disease were shorter (men 171.4 +/- 9.0 cm vs 176.4 +/- 6.9 cm, P<0.01; women 159.7 + 7.3 cm vs 162.7 +/- 6.2 cm, P<0.01) and had a higher prevalence of symptomatic osteoporosis (5%) cancer (10%), and autoimmune disease (25%). Compared with matched controls and with patients whose celiac disease had been diagnosed during childhood (n=36), or who had remained symptom-free (n=95), patients who had undiagnosed symptomatic celiac disease during childhood exhibited higher prevalence of short stature (26%), low female fertility or low birth weight (36%). Multivariate analysis showed that short stature and low fertility correlated with duration of symptoms before diagnosis; osteoporosis and cancer correlated with age. The prevalence of autoimmune disease was unrelated to early onset of symptoms or delay to diagnosis. CONCLUSIONS: Missing the diagnosis of celiac disease in a symptomatic child may lead to short stature and low female fertility.

Adolescent↗
PubMed1999

Tissue transglutaminase antibodies in celiac disease.

OBJECTIVE: Tissue transglutaminase is the antigen for antiendomysial antibodies, whose power in screening for celiac disease is well known. Our aim was to assess the efficacy of an ELISA assay for tissue transglutaminase antibodies. METHODS: Tissue transglutaminase antibodies were analyzed in serum from 39 untreated celiac disease patients and 61 controls. Tissue transglutaminase was used as antigen, and test sera analyzed by ELISA. Results higher than 0.6 optical density were considered positive, lower than 0.4 negative, and between 0.4 and 0.6 borderline. RESULTS: Optical density of the serum from the patients with untreated celiac disease (median: 1.41; range: 0.33-1.47) were significantly higher than the controls (median: 0.32; range: 0.17-0.68; p < 0.0001; 95% confidence interval 0.87-1.08). Thirty-three patients with untreated celiac disease were positive, 4 borderline, and 2 negative. Fifty-five controls were negative, 4 borderline, and 2 positive. If we consider borderline results to be positive, sensitivity is 94.8% and specificity 90.1%. None of the controls gave results higher than 0.7 optical density. Apart from the 2 negative patients with untreated celiac disease, the two groups overlapped only between 0.4 and 0.7 optical density. CONCLUSIONS: Because of the high sensitivity (approximately 95%) and technical simplicity, tissue transglutaminase antibodies may prove useful for the screening of celiac disease in population at low or medium risk of celiac disease. To avoid duodenal biopsies in patients without celiac disease, the specificity of the screening procedure may be increased by confirming with antiendomysial antibodies by immunofluorescence on human umbilical cord in individuals with results between 0.4 and 0.7 optical density.

Adolescent↗
PubMed1989

[The role of disorders of secretion of pancreatic enzymes and bile and bacterial contamination of the small intestine in the pathogenesis of diarrhea in patients with celiac disease].

The study of 53 patients with celiac disease provided evidence for the impotent role of the inhibited hyposecretion of pancreatic enzymes, atony of the gallbladder responsible for abnormal bile acids introduction into the intestinal lumen in digestion, elevated concentrations of free bile acids at the expense of lowjugated ones in duodenal and jejunal contents as well as bacterial dissemination of the proximal portion of the small intestine in pathogenesis of diarrhea observed in celiac disease. It is concluded that inclusion of continuous courses of enzyme preparations and light cholagogues in the treatment schemes of celiac disease and administration in its exacerbation of adsorbents, astringents, antibacterial preparations should be necessary therapeutic measures.

Amylases↗
PubMed1986

Intestinal mast cells in different stages of celiac disease.

A study of mast cell content of the small intestinal mucosa in children with celiac disease is presented. Twenty patients with true celiac disease were studied and compared with 7 patients with transient gluten intolerance and 20 normal control patients. In healthy children we found (mean +/- SE) 142.5 +/- 16.4 mast cells/mm2. In children with active celiac disease, only 40.1 +/- 19.5 cells were found. This difference was highly significant (P less than 0.001). On a gluten-free diet for 1.5 years, the number of mast cells was 82.2 +/- 27.2/mm2 and still remained significantly depressed (P less than 0.001). Upon gluten challenge in celiac disease, the numbers fell to 58.3 +/- 32.6/mm2, while in transient gluten intolerance the numbers of mast cells attained were 102.5 +/- 22.5/mm2, near normal values. These findings indicate that during the untreated phase of celiac disease the number of mast cells is depressed. On a gluten-free diet, the number rises but does not reach normal control levels even after prolonged remission. It is suggested that even during remission of celiac disease the mast cells continue to be damaged by unidentified toxic agents.

Biopsy↗
PubMed1999

Antibodies to gliadin, endomysium, and tissue transglutaminase for the diagnosis of celiac disease.

BACKGROUND: Tissue transglutaminase has recently been identified as the main autoantigen recognized by antiendomysial antibodies in celiac disease. Serum immunoglobulin (Ig)A antibodies to tissue transglutaminase (tTG-ab) determined by an enzyme-linked immunosorbent assay (ELISA) technique have been reported to correlate closely with IgA antiendomysial antibodies (EMA). The purpose of this study was to assess the sensitivity, specificity, and predictive value of tTG-ab measured by a commercially available ELISA technique, compared with those of EMA and IgA antigliadin antibodies (AGA) for the diagnosis of celiac disease. METHODS: Twenty-seven serum samples were obtained from patients with untreated celiac disease, 37 from patients who had had gluten withdrawn from their diets for varying time spans, and 34 from control subjects without celiac disease. All were younger than 14 years. Presence of tTG-ab and AGA was determined by ELISA and of EMA by indirect immunofluorescence. RESULTS: Twenty-six of 27 serum samples obtained from patients at the time of diagnosis of celiac disease were AGA positive. All 27 (concordance rate 100%) were positive for EMA and tTG-ab. Of the 34 control subjects, 1 was for AGA and 2 for tTG-ab. All 34 were negative for EMA. Sensitivity, specificity, positive predictive value, and negative predictive value within this group were, for tTG-ab: 100%, 94%, 93%, and 100%, respectively; for EMA: all four indexes were 100%; and for AGA: 96%, 97%, 96%, and 97%, respectively. Of the 37 with treated celiac disease, 2 were AGA positive, 9 were EMA positive, and 6 were tTG-ab positive. The concordance rate between EMA and tTG-ab was 100% in the group with untreated celiac disease, 94% in the control subjects, and 76% in the group with treated celiac disease. CONCLUSIONS: Immunoglobulin A antibodies to tissue transglutaminase are new, highly sensitive, and specific markers of celiac disease. They can be determined easily by an accurate, comparatively cheap technique and thereby may advantageously replace the EMA marker traditionally used.

Adolescent↗