Gluten Withdrawal Research Articles

Coeliac disease associated with Sjögren’s syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren’s syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

Coeliac disease associated with Sj�gren?s syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism

<h2>Abstract</h2> Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

The iceberg cometh: Establishing the prevalence of celiac disease in the United States and Finland

The iceberg cometh: Establishing the prevalence of celiac disease in the United States and Finland

Affective disorders and quality of life in adult coeliac disease patients on a gluten-free diet.

Psychiatric symptoms, common in untreated coeliac disease patients, may improve after gluten withdrawal. To estimate the incidence of psychiatric disorders in coeliac disease patients on gluten withdrawal and to evaluate: (1) the psychological weight of a chronic disease that involves a restrictive diet and a limited life style; (2) the acceptance of the disease; (3) the effects of both disease and diet on behaviour and quality of life. Three groups of 100 patients (coeliac disease patients, diabetic patients and healthy controls, respectively) were assessed by means of a professional semi-structured diagnostic interview based on DSM-IV criteria. This interview, together with specific psychiatric questionnaires, ruled out axis I or II psychopathological disturbances. The modified Self-rating Depression Scale and State and Trait Anxiety Inventory Y2 scores were significantly higher in both coeliac and diabetic patients than in healthy controls. The duration of gluten restriction was related to significantly higher modified Self-rating Depression Scale scores in patients with a more recent diagnosis. Quality of life was poorer in both coeliac and diabetic patients than in healthy controls and significantly correlated with anxiety. The Illness Behaviour Questionnaire showed a high psychological and somatic perception of illness in both coeliac and diabetic patients. Its subscale scores correlated significantly with anxiety and depression symptoms. In coeliac disease, affective disorders should be ascribed to difficulties in adjusting to the chronic nature of the disease rather than directly to the disease itself, thus giving an indication for preventive liaison psychiatric interventions.

Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease.

Gluten-free diet (GFD) plays a key role in the treatment of celiac disease (CD), but it is difficult to evaluate the effect of GFD on the improvement of villous architecture using sensitive, non-invasive tests. Aim of this study is to evaluate anti-transglutaminase (tTG) antibodies in the follow-up of CD to detect histologic recovery. We studied 42 consecutive patients with CD. In all the patients anti-tTG antibodies (evaluated by the enzyme linked immunosorbent assay method) and EGDscopy with multiple bioptic samples before GFD and then 6, 12, and 18 months after GFD were evaluated. For comparison, a sorbitol H2-breath test (H2-BT) and anti-endomysium (EMA) antibodies test were carried out concomitantly. Anti-tTG results were positive in 36 of 42 patients before GFD (80.95%), while they were positive in 11 of 34 (32.35%), 1 of 17 (5.88%), and 0 of 6 (0%) of patients with a persistence in histologic lesions 6, 12, and 18 months of GFD respectively, without any correlation with persistence of histologic lesions (P = NS). Also EMA failed to show correlation with improvement of histologic lesions. They were positive in 31 of 42 patients before GFD (73.80%), while they were positive in 18 of 34 (52.94%), 3 of 17 (17.64%), and 0 of 6 (0%) cases 6, 12, and 18 months of GFD respectively (P = NS). Regarding sorbitol H2-BT, it was positive in 40 of 42 (95.24%) patients before GFD, while it was positive in 31 of 34 (91.17%), 13 of 17 (76.47%), and 4 of 6 (50%) of patients with a persistence in histologic lesions 6, 12, and then 18 months after GFD starting (see Fig. 2, infra). So, anti-tTG and EMA were ineffective in assessing the histologic recovery at each follow-up visit (P = NS), while sorbitol H2-BT seems more effective than anti-tTG and EMA in this field (P < 0.0001 sorbitol H2-BT versus anti-tTG and versus EMA at 18 months after gluten withdrawal). Thirty-eight of 42 (90.47%) patients adhered to a strict GFD. Four patients were found to have occasional dietary transgression, and in all we noted a progressive decreasing of anti-tTG after 6 months of GFD and negative anti-tTG after 12 months of GFD, but sorbitol H2-BT persisted being positive during the entire follow-up. Intestinal damage persisted during the follow-up, despite anti-tTG and EMA negativity, and worsened in the presence of dietary lapses. Anti-tTG does not seem effective to assess histologic recovery in the follow-up of celiac patients after they have started GFD due to its poor correlation with histologic damage.

High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal

Objective Celiac disease is a gluten-sensitive enteropathy with a broad spectrum of clinical manifestation, and most celiac patients respond to a gluten-free diet (GFD). However, in some rare cases celiacs continue to experience GI symptoms after GFD, despite optimal adherence to diet. The aim of our study was to evaluate the causes of persistence of GI symptoms in a series of consecutive celiac patients fully compliant to GFD. Methods We studied 15 celiac patients (five men, 10 women, mean age 36.5 yr, range 24–59 yr) who continued to experience GI symptoms after at least 6–8 months of GFD (even if of less severity). Antigliadin antibody (AGA) test, antiendomysial antibody (EMA) test, and sorbitol H2-breath test (H2-BT), as well as esophagogastroduodenoscopy (EGD) with histological evaluation, were performed before starting GFD. Bioptic samples were obtained from the second duodenal portion during EGD, and histopathology was expressed according to the Marsh classification. To investigate the causes of persistence of GI symptoms in these patients, we performed AGA and EMA tests, stool examination, EGD with histological examination of small bowel mucosa, and sorbitol-, lactose-, and lactulose H2-breath tests. Results Histology improved in all patients after 6–8 months of GFD; therefore, refractory celiac disease could be excluded. One patient with Marsh II lesions was fully compliant to his diet but had mistakenly taken an antibiotic containing gluten. Two patients showed lactose malabsorption, one patient showed Giardia lamblia and one patient Ascaris lumbricoides infestation, and 10 patients showed small intestinal bacterial overgrowth (SIBO) by lactulose H2-BT. We prescribed a diet without milk or fresh milk–derived foods to the patient with lactose malabsorption; we treated the patients with parasite infestation with mebendazole 500 mg/day for 3 days for 2 consecutive wk; and we treated the patients with SIBO with rifaximin 800 mg/day for 1 wk. The patients were re-evaluated 1 month after the end of drug treatment (or after starting lactose-free diet); at this visit all patients were symptom-free. Conclusions This study showed that SIBO affects most celiacs with persistence of GI symptoms after gluten withdrawal.

High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal.

Celiac disease is a gluten-sensitive enteropathy with a broad spectrum of clinical manifestation, and most celiac patients respond to a gluten-free diet (GFD). However, in some rare cases celiacs continue to experience GI symptoms after GFD, despite optimal adherence to diet. The aim of our study was to evaluate the causes of persistence of GI symptoms in a series of consecutive celiac patients fully compliant to GFD. We studied 15 celiac patients (five men, 10 women, mean age 36.5 yr, range 24-59 yr) who continued to experience GI symptoms after at least 6-8 months of GFD (even if of less severity). Antigliadin antibody (AGA) test, antiendomysial antibody (EMA) test, and sorbitol H2-breath test (H2-BT), as well as esophagogastroduodenoscopy (EGD) with histological evaluation, were performed before starting GFD. Bioptic samples were obtained from the second duodenal portion during EGD, and histopathology was expressed according to the Marsh classification. To investigate the causes of persistence of GI symptoms in these patients, we performed AGA and EMA tests, stool examination, EGD with histological examination of small bowel mucosa, and sorbitol-, lactose-, and lactulose H2-breath tests. Histology improved in all patients after 6-8 months of GFD; therefore, refractory celiac disease could be excluded. One patient with Marsh II lesions was fully compliant to his diet but had mistakenly taken an antibiotic containing gluten. Two patients showed lactose malabsorption, one patient showed Giardia lamblia and one patient Ascaris lumbricoides infestation, and 10 patients showed small intestinal bacterial overgrowth (SIBO) by lactulose H2-BT. We prescribed a diet without milk or fresh milk-derived foods to the patient with lactose malabsorption; we treated the patients with parasite infestation with mebendazole 500 mg/day for 3 days for 2 consecutive wk; and we treated the patients with SIBO with rifaximin 800 mg/day for 1 wk. The patients were re-evaluated 1 month after the end of drug treatment (or after starting lactose-free diet); at this visit all patients were symptom-free. This study showed that SIBO affects most celiacs with persistence of GI symptoms after gluten withdrawal.

First Steps in Unraveling the Genotype of Enteropathy-Type T-Cell Lymphoma

First Steps in Unraveling the Genotype of Enteropathy-Type T-Cell Lymphoma

Thyroid autoimmunity in childhood celiac disease.

Celiac Disease is associated with other autoimmune disorders, but much greater emphasis has been put on the association of celiac disease with Type 1 Diabetes Mellitus (T1DM) than on its association with autoimmune thyroiditis even though the high prevalence of anti-thyroid antibodies (1–3) and thyroid disorders (4) in celiac patients suggests that this association may be clinically more important. From Medline (1980–2001) we found 176 papers on the association between CD and T1DM but only 36 on its association with thyroid disorders. We prospectively studied the prevalence of anti-thyroid antibodies in celiac children. In children with increased titers we measured thyroid hormones and TSH and performed thyroid ultrasonography. PATIENTS AND METHODS We studied 66 children with CD (35 females, 31 males) diagnosed with jejunal biopsy according to the European Society of Paediatric Gastroenterology and Nutrition criteria. Forty-one children were untreated and on a gluten-containing diet. Serum samples were obtained the same day of the first duodenal biopsy. Nineteen children were on a gluten-free diet and 6 children were on a short (median 3 months) gluten-challenge to confirm the diagnosis. Serum titres of TPO and TG were measured, and when raised we measured FT3, FT4, and TSH, and performed thyroid ultrasonography using a 7.5-MHz linear probe. Thyroid patterns were classified according to Sostre criteria (5). Follow up sera after a gluten-free diet of 3 months to 15 years were retested for TPO and TG in 30 children. RESULTS AND CONCLUSION Of the 41 untreated celiac children, six (14.6%) had raised TPO, three raised TG titers, and one had elevated TSH (Table 1). Ultrasonography showed a normal thyroid gland in three children, multiple hypoechoic foci in a normoechoic gland (grade 2) in two children, and an enlarged gland with diffuse but mild hypoechogenicity (grade 3) in one child. FT3 and FT4 were always normal.TABLE 1: Characteristics of children with anti-thyroid antibodiesFollow-up sera of these 6 children were obtained after a strictly conducted gluten-free diet of variable duration (range 1–5 years) with serial determination of anti-gliadin and anti-endomysium antibodies that were always negative. TPO became negative in two, but titers increased in the other four, and TSH was elevated in one more child (Table 1). There was an associated T1 DM in one child, a family history of type T1 DM in another, and a celiac mother in two children, suggesting that association with autoimmune disease in the family may be a risk factor. Interestingly, at diagnosis untreated children with anti-thyroid antibodies were significantly older (median age 7.5 vs. 2.0 years in children without antibodies, P = 0.03 Mann-Whitney U test) and of those younger than 6 years only 1/23 (4.3%) had anti-thyroid antibodies, whereas over 6 years 5/18 were positive (27.7%, P = 0.04), suggesting that duration of gluten exposure may be another important risk factor for the development of thyroid autoimmunity. Of the children with anti-thyroid antibodies, the younger three had lower titres. Ultrasound showed a normal gland in all, and in two, TPO became negative after instituting a gluten-free diet. The older three children with anti-thyroid antibodies had higher TPO titres which increased after a gluten-free diet. Ultrasonography showed structural damage of the gland, and two became sub-clinically hypothyroid with an elevated TSH, and were given replacement treatment with L-thyroxin. Of the 25 treated celiac children, on gluten-free diet or after a short challenge, none had anti-thyroid antibodies. Their median age at diagnosis was 1.5 years. We also had a chance to diagnose CD in seven young adults, four medical students, and three mothers of our celiac children (age-range 23–33 years) and four of them had anti-thyroid antibodies. Our data are in agreement with other studies reporting a correlation between a late diagnosis of CD, which mirrors longer gluten exposure, and the prevalence of autoimmune thyroid antibodies (1,2), but suggest that a gluten-free diet is not sufficient to suppress thyroid autoimmunity when it has already started. Perhaps an early diagnosis and an early gluten withdrawal may be preventive for thyroiditis.

Celiac disease in autoimmune cholestatic liver disorders.

In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

Celiac disease in autoimmune cholestatic liver disorders

OBJECTIVES: In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. METHODS: Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. RESULTS: Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. CONCLUSIONS: The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

Red cell distribution width as a marker of coeliac disease: a prospective study.

Coeliac disease is frequently underdiagnosed because of its protean presentations. Serological tests may be helpful in screening programmes for populations at risk, but they are costly. To determine prospectively whether a commonly available haematological test such as the red cell distribution width (RDW) could be of help in detecting unrecognized coeliac disease. Of 353 consecutive adult patients referred to our outpatient malabsorption clinic, 198 in whom clinical suspicion was strong were referred for further investigations and intestinal biopsy. Seventy-six inflammatory bowel disease outpatients and 90 subjects admitted for diseases other than malabsorption were enrolled as the control group. RDW was increased in 94 (47.4%) and normal in 104 (52.5%) of 198 patients. Duodenal biopsy confirmed coeliac disease in 80 (85.1%) of the former patients and 69 (66.3%) of the latter patients. No correlation between RDW values and histological scores was found. Overall RDW increase was found in 80/149 (53.7%) patients with a definite diagnosis of coeliac disease, and in 14/49 (28.6%) patients in whom biopsy excluded the disease. A 1-year gluten withdrawal led to a significant decrease in RDW value, even in patients with obdurate mucosal impairment. In patients in whom there is a strong clinical suspicion of coeliac disease, an elevated RDW despite normal haemoglobin concentration may be a reliable predictor of the disease.

Immunohistochemical Analysis of ZO-1 in the Duodenal Mucosa of Patients with Untreated and Treated Celiac Disease

Background/Aim: ZO-1 is a good marker for tight junction integrity which may be damaged in many intestinal diseases. ZO-1 can also accumulate in the cellular nucleus in addition to sites of cell-cell contact, suggesting a potential role in cellular proliferation and differentiation. We evaluated the expression and distribution of ZO-1 in patients with celiac disease before and after a gluten-free diet. Methods: The ZO-1 expression was evaluated semiquantitatively by means of immunohistochemical analysis in duodenal bioptic specimens of 10 consecutive patients with celiac disease before and after a gluten-free diet and in 10 controls. Furthermore, the nuclear staining was analyzed quantitatively, evaluating 3,000 cells for each count, and it was expressed as a percentage of labeled nuclei over the total of analyzed cells. Results: The intestinal mucosa of untreated celiac disease patients shows a globally lower ZO-1 labeling than that of controls. The expression of ZO-1 in the treated celiac mucosa did not differ significantly from normal intestinal mucosa of healthy subjects. At the crypt level of untreated celiac mucosa, a low intensity of nuclear labeling (1.75 ± 0.32%) was found, while in both treated celiac disease patients and in normal subjects we observed a statistically significant higher percentage of strongly labeled nuclei (53.72 ± 6.30% and 56.79 ± 5.45%, respectively; p = 0.0002). Conclusions: Our data show a global underexpression of ZO-1 in the duodenal mucosa of active celiac disease patients. Gluten withdrawal allows a normalization of the ZO-1 expression in treated celiac disease patients. Furthermore, the particular pattern of ZO-1 resembles the cellular distribution in undifferentiated cells and may be the result of immaturity of the enterocytes in untreated celiac sprue.

Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome

Abdominal symptoms in the absence of mucosal abnormalities are features of both the irritable bowel syndrome (IBS) and latent/potential celiac disease (cd). To identify a possible subgroup of IBS patients with latent/potential cd, surrogate markers of cd were investigated in IBS patients. IBS patients suffering from diarrhea (n = 102), and patients with active cd (n = 10), treated cd (n = 26), and latent cd (n = 5) were included in the study. We measured serum immunoglobulin (Ig) A against gliadin and tissue-transglutaminase, and IgA and IgM against gliadin, tissue-transglutaminase (intestinal cd-associated antibodies), and the dietary proteins beta-lactoglobulin and ovalbumin in duodenal aspirate by enzyme-linked immunosorbent assay. Intraepithelial lymphocytes (IELs) were counted in histology sections, and the expression of HLA-DQ2 (A1*0501/B1*0201) was investigated by polymerase chain reaction. In 26 IBS patients, the effect of 6 months of gluten withdrawal was examined. Most cd patients expressed HLA-DQ2 and had increased intestinal cd-associated antibodies, whereas cd-associated serum IgA and IEL counts were increased in active cd in contrast to treated or latent cd. In IBS patients, 35% were HLA-DQ2-positive, 23% had increased IEL counts, and 0% and 30% had increased cd-associated antibodies in serum and duodenal aspirate, respectively. Furthermore, stool frequency and intestinal IgA decreased significantly under a gluten-free diet in the subgroups of HLA-DQ2-positive and intestinal antibody-positive IBS patients when compared with IBS patients without these markers. HLA-DQ2 expression and increased intestinal cd-associated antibodies are markers that can identify latent/potential cd in a subgroup of IBS patients who consequently appear to profit from a gluten-free diet.

Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders

BACKGROUND AND AIMSDuration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual...

Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study

OBJECTIVES: Many afflictions have been associated with celiac disease, but chance associations may exists. The aim of this study was to establish, by means of a multicenter prospective study, the prevalence of thyroid impairment among adult patients with newly diagnosed celiac disease and to evaluate the effect of a 1-yr gluten withdrawal on thyroid function. METHODS: A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies. RESULTS: Thyroid disease was 3-fold higher in patients than in controls ( p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later. CONCLUSIONS: The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.

Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.

Many afflictions have been associated with celiac disease, but chance associations may exists. The aim of this study was to establish, by means of a multicenter prospective study, the prevalence of thyroid impairment among adult patients with newly diagnosed celiac disease and to evaluate the effect of a 1-yr gluten withdrawal on thyroid function. A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies. Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later. The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.

Increased intestinal intra-epithelial T lymphocytes in primary glomerulonephritis: a role of oral tolerance breakdown in the pathophysiology of human primary glomerulonephritides?

There is increasing evidence that some organ-specific and generalized autoimmune diseases in humans might be related to a breakdown of oral tolerance. We explored this hypothesis in human primary glomerulonephritides. We prospectively counted intraepithelial T lymphocytes in the duodenal mucosa (as a marker of rupture of oral tolerance), together with IgA1 and IgA2 mucosal plasma cells, in patients with primary glomerulonephritides. We investigated eight adults with immune-complex glomerulopathy (membranous nephropathy+membranoproliferative glomerulonephritis), 16 adults with an idiopathic nephrotic syndrome, and 25 adults with IgA nephropathy. Patients with glomerulonephritides were compared to two control groups: group 1 consisted of nine healthy adults; group 2 comprised five adults with coeliac disease before dietary gluten withdrawal or during a clinical relapse related to gluten ingestion. (The latter disease is associated with increased numbers of intraepithelial T lymphocytes, and a breakdown of oral tolerance to gliadins is involved in the pathogenesis of coeliac disease). Duodenal fibroscopy was performed under neuroleptanalgesia. Four to six endoscopic biopsy specimens were taken from the second duodenum. Intraepithelial T lymphocytes were blindly counted on paraffin sections stained with haematein-eosin-saffron (HES), within the epithelium of a villus in a zone with at least 100 cells. Mucosal IgA1 and IgA2 plasma cells were blindly counted in a mucosal tissue unit by using specific mouse monoclonal antibodies directed against IgA1 and IgA2, with alkaline phosphatase anti-alkaline phosphatase (APAAP) revelation. As values were not normally distributed, we used non-parametric analysis of variance with the Kruskal-Wallis test, and compared median values by using the non-parametric Mann-Whitney test. Intraepithelial T lymphocytes were significantly more abundant in patients with primary glomerulonephritides and coeliac disease than in healthy controls (P < 0.0001 in the Kruskal-Wallis test): healthy controls, median 11 (range 4.65-16); immune complex glomerulopathy, 27.45*** (15-93); idiopathic nephrotic syndrome, 16.5** (9-26.5); IgA nephropathy, 26.10*** (11.3-47.5); coeliac disease, 55*** (20-80) (*P <0.05; **P <0.01; ***P < 0.005, Mann-Whitney test). No difference was found in the number of duodenal IgA1 and IgA2 plasma cells between controls and patients with primary glomerulonephritides. IgA1 and IgA2 plasma cells were increased in patients with coeliac disease. The significant increase in intestinal intraepithelial T lymphocytes in primary glomerulonephritides suggests a pathophysiological role of oral tolerance breakdown.

Body composition and dietary intakes in adult celiac disease patients consuming a strict gluten-free diet

Celiac disease responds to dietary gluten withdrawal, but data on the long-term effects of gluten-free diets are discordant. Our aim was to evaluate the nutritional status and body composition of adult celiac disease patients consuming a gluten-free diet who were in clinical, biochemical, and histologic remission. We studied 71 patients (51 women and 20 men; mean age: 27 y; range: 17-58 y) and 142 healthy control subjects matched by sex and age. The subjects' height, weight, body mass index, fat and lean mass, and bone mineral content (evaluated by dual-energy X-ray absorptiometry) were measured; a 3-d dietary questionnaire was administered; and total daily energy, fat, carbohydrate, and protein intakes were calculated. The weight, height, and body mass index of male celiac disease patients and the weight and body mass index of female celiac disease patients were significantly lower than the corresponding measurements in control subjects. The fat and lean mass of both male and female patients was significantly different from that of control subjects; however, bone mineral content was significantly lower only in females in whom celiac disease was diagnosed in adulthood. Total energy intake was lower in the patients than in the control subjects (9686 +/- 1569 and 11297 +/- 1318 kJ/d in males and 6736 +/- 1318 and 7740 +/- 1715 kJ/d in females), and the diet of the patients was unbalanced, with a higher percentage of energy as fat and a lower percentage of energy as carbohydrates. Although strictly compliant with their gluten-free diet and in complete remission, patients with celiac disease showed differences in body composition and dietary intakes compared with control subjects. Strict follow-up and dietary advice in terms of the choice and composition of foods seem necessary to prevent malnutrition.

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

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. patients affected by celiac disease have a markedly delayed gastric emptying of solids, which returns to normal after gluten withdrawal.