Positive Antiendomysial Antibodies Research Articles

Factors contributing to high levothyroxine doses in primary hypothyroidism: an interventional audit of a large community database.

While few hypothyroid patients require more than the expected weight-related dose of levothyroxine, the underlying causes of larger-than-expected dosing requirements have not been studied in a single cohort. Our aim was to determine and quantify the multiple factors contributing to high-dose levothyroxine requirements in a cohort of patients with hypothyroidism. The Grampian Automated Follow-Up Register (GAFUR) monitors around 17,500 hypothyroid patients. In 2008, 190 (1%) patients took >225 μg of levothyroxine daily. A questionnaire was sent to 174 patients (16 were untraceable) to assess causes and to offer blood tests for endomysial, parietal cell (PCA), and thyroid peroxidase (TPO) autoantibodies. Primary care practices were contacted for medication details. All patients with positive endomysial autoantibodies were referred to a gastroenterologist. Thyroid function tests and levothyroxine doses were re-evaluated in 2011. A total of 125 questionnaires (72%) were returned. Mean levothyroxine dose was 248 μg daily. Twenty-six patients (20.8%) took medication known to interfere with levothyroxine absorption, and 21 patients (16.8%) admitted to compliance issues. Seven patients had positive anti-endomysial antibodies on initial screening, with four being new diagnoses of celiac disease, and PCA were positive in 27 (21.6%) patients. At follow-up in 2011, the mean levothyroxine dose had decreased in patients on interfering medications and in the four new cases of celiac disease. Causes of patients needing high-dose levothyroxine replacement include poor compliance, medication interference, PCA (as a marker of atrophic/autoimmune gastritis), and celiac disease. Doses can be decreased following advice regarding medication or after management of underlying conditions.

The presence of anti-endomysial antibodies and the level of anti-tissue transglutaminases can be used to diagnose adult coeliac disease without duodenal biopsy.

The new ESPGHAN guidelines for diagnosis of paediatric coeliac disease suggest to avoid biopsy in genetically pre-disposed and symptomatic individuals with positive anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTG). However, duodenal biopsy remains the gold standard in adult coeliac disease. To establish the cut-off values of a-tTG, which would: predict the presence of duodenal histology (Marsh ≥2) diagnostic for coeliac disease; and predict the presence of villous atrophy (Marsh 3) in adults. We performed an observational prospective study including all consecutive adult patients with suspected coeliac disease. All subjects were tested for EMA and a-tTG. Coeliac disease diagnosis was made in presence of Marsh ≥2, a-tTG >7 U/mL and positive EMA. A ROC curve was constructed to establish the best specificity cut-off of a-tTG levels, which would predict the presence of Marsh ≥2 and Marsh 3 at histology. The study included 310 patients with positive antibodies. Histology showed Marsh 1 in 8.7%, Marsh 2 in 3.5%, Marsh 3 in 87.7%. The best cut-off value of a-tTG for predicting Marsh ≥2 was 45 U/mL (sensitivity 70%; specificity 100%; PPV 100%; NPV 24.1%); the best cut-off for predicting villous atrophy was 62.4 U/mL (sensitivity 69%, specificity 100%; PPV 100%; NPV 31%). The diagnosis of coeliac disease can be reached without histology in adult patients with positive EMA and a-tTG levels >45 U/mL. An a-tTG level >62.4 was diagnostic for villous atrophy. These results could contribute to improving the diagnosis of coeliac disease by allowing for a significant reduction in diagnosis-related costs.

An uncommon diagnosis of celiac disease in a thalassemic girl

s / Digestive and Liver Disease 46 (2014) e85–e127 e117 AN UNCOMMON DIAGNOSIS OF CELIAC DISEASE IN A THALASSEMIC GIRL Monica Montuori1,∗, Maria Paola Smacchia2, Donatella Iorfida1, Stefania Leoni1, Chiara Maria Trovato1, Silvia Gatti 1, Ilaria Celletti 1, Francesco Valitutti 1, Michela Capogna2, Caterina Anania1, Salvatore Cucchiara1 1 UOC Gastroenterologia ed Epatologia Pediatrica, Sapienza Universita di Roma, Roma, Italy 2 Presidio Regionale Malattie Ereditarie, Sapienza-Universita di Roma, Roma, Italy Celiac disease (CD) has a heterogeneous clinical expression. This report describes an uncommon CD diagnosis in a 21 year old girl, affected by thalassemia major and followed at our Hematology Unit. Her ferritin levels used to range between 700 and 1000 g/L when she was on deferoxamine (40mg/kg/day s.c.), therefore replaced with deferosilax (30–40mg/kg/day per os) with stabilization of values around 400 g/L. After EBV infection, recurrent abdominal pains and diarrhea appeared. Few months later, ferritin levels decreased stepwise to 120 g/L albeit the same daily iron intake (blood transfusions) and the same drug dose, leading hematologists to reduce deferosilax up to 13mg/kg/day. Her values increased up to 300 g/L. Thereafter, she was sent at our Gastroenterology and Hepatology Unit because of persisting gastrointestinal symptoms. Screening for CD showed anti-transglutaminase IgA>100UA/mL (<16) and positive antiendomysial antibodies. A reduction in number and height of foldswas found in bulb and duodenum at upper gastrointestinal endoscopy and histological examination confirmed CD diagnosis (MarshOberhuber 3a-3b). Once on gluten-free diet (GFD) ferritin levels rose to 568 g/L, thus requiring to increase deferosilax dose. This report suggests to consider undiagnosedCD in thalassemic patients when ferritin levels unexpectedly decrease demanding a lower iron chelator dose, perhaps due to un underlying malabsorption. Although the GFD leads to increased ferritin levels, it remains essential in order to prevent the risk of CD complication in organs such as liver, pancreas, thyroid, bone and heart, already potentially damaged by hematological condition. http://dx.doi.org/10.1016/j.dld.2014.07.138 A CASE OF ASYMPTOMATIC GASTRITIS NODULAR HP-RELATED AND COELIAC DISEASE Elvira Difrancisca ∗, Maria Letizia Lospalluti, Giuseppe Iacono Azienda Ospedaliera di Rilievo Nazionale ad Alta SpecializzazioneCivico, G. Di Cristina Benfratelli,

Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios

Introduction. Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. Aim. We wanted to test the uniformity of application of Marsh–Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. Methods. We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh–Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. Results. Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. Discussion. Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh–Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.

Validation of point-of-care testing for coeliac disease in children in a tertiary hospital in north India

ObjectiveSome of the conventional serological tests for coeliac disease (CD) are expensive, time-consuming and not readily available in developing countries, leading to a delay in diagnosis. Recently, point-of-care tests (POCT)...

Dramatic improvement of parkinsonian symptoms after gluten-free diet introduction in a patient with silent celiac disease

Dear Sirs, Celiac disease (CD) may manifest only with neurological symptoms [5], even in advanced age [3]. No clear association has been reported to date between CD and Parkinson’s disease (PD). A 75-year-old man presented with a 1-year history of difficulty with walking, instability, and fatigability. Neurological examination showed facial hypomimia, bradykinesia, rigidity, and postural instability with a UPDRS/Part II score of 8 and a UPDRS/part III motor score of 19 (Table 1). The remaining neurological examination was unremarkable. The patient had never been treated with drugs acting on the central nervous system; in particular he had never received drugs causing parkinsonism such as neuroleptics. Brain MR revealed several nonspecific foci of hyperintensity in the frontal and parietal subcortical white matter but not in the basal ganglia. Few punctate calcifications were present in the globus pallidus bilaterally, a finding that is quite common in elderly subjects [6]. Singlephoton emission computed tomography (SPECT) after intravenous injection of 185 MBq of I-FP-CIT (DaTSCAN, G.E. Healthcare, UK) showed a pronounced decrease of radiotracer uptake in the left putamen and moderate decrease in the contralateral putamen (Fig. 1). Activity was clearly visible in the caudate nuclei of both hemispheres. Semi-quantitative analysis confirmed visual assessment of images: putamen-to-occipital cortex uptake ratios were lower than values obtained in healthy subjects, and the reduction was more pronounced on the left hemisphere. On the basis of clinical and SPECT data, a diagnosis of Parkinson’s disease was made. Laboratory studies revealed reduced serum folate level (2.8 ng/ml, n.v. 3–15) and hyperhomocysteinemia (23.4 lmol/l, n.v. 5–15), but vitamin B12 level was normal. The possibility of asymptomatic malabsortion due to a silent CD was explored. Serological screening revealed anti-gliadin antibodies, markedly elevated IgA (236 U/ml, n.v.\ 20) and IgG (86 U/ml; n.v. \ 20), anti-transglutaminase antibodies, and positive anti-endomysial antibodies. Duodenal histology was diagnostic of CD. The gastroenterologist prescribed a gluten-free diet. The patient came back to the neurological outpatient clinic only 3 months after the beginning of the gluten-free diet: during this period he had no pharmacological treatment for PD, but he reported an almost complete remission of symptoms. The improvement was confirmed by neurological evaluation, with a UPDRS/Part II score of 3 and a UPDRS/part III motor score of 8 (Table 1). Because of this improvement, we decided not to treat the patient at this stage. In order to define whether the gluten-free diet had modified striatum dopaminergic activity, we repeated the SPECT study 8 months after diet onset. SPECT confirmed the previous abnormalities and showed a further decrease in radiotracer uptake in the putamen bilaterally. Activity V. Di Lazzaro (&) F. Capone F. Ranieri Department of Neurosciences, Institute of Neurology, Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128 Rome, Italy e-mail: v.dilazzaro@unicampus.it

Diagnosis of Coeliac Disease in Children Younger Than 2 Years

To diagnose coeliac disease (CD) in children younger than 2 years, the old ESPGHAN criteria based on 3 small bowel biopsies were recommended until recently. The aim of the present study was to investigate the applicability of only 1 small intestinal biopsy plus positive serology for the diagnosis of CD in children younger than 2 years. A prospective cohort study included 81 patients younger than 2 years with symptoms suggestive of CD, who all completed the diagnostic procedure based on 3 small bowel biopsies. According to the finding of the third biopsy, patients were divided into group A-CD confirmed (N = 44), and group B-CD not confirmed, after the gluten challenge (N = 37). At the time of the first biopsy, total villous atrophy (Marsh IIIc) was found more often in group A than in group B (77% vs 27%, P < 0.01). Also, all of the studied antibodies were more frequently positive in group A than in group B (P < 0.01 for all of the tested antibodies). Positive anti-endomysial antibodies and Marsh IIIc finding were the best discriminators between the group A and the group B and considerably contributed to the prediction of CD. The second and the third biopsies (before and after the gluten challenge) may also be avoided when diagnosing CD in children younger than 2 years provided that the child, at the time of presentation, has positive anti-endomysial antibodies and Marsh IIIc on the small bowel biopsy. A gluten challenge should be still considered in all other children younger than 2 years.

Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture.

55. Seasonal variation in lymphocytic gastritis not associated with coeliac disease or helicobacter infection

<h3>Introduction</h3> Lymphocytic gastritis (LG) is an inflammatory condition of the gastric mucosa characterised by an intraepithelial lymphocyte count >25 per 100 epithelial cells. Coeliac disease (CD) and Helicobacter pylori infection (HP) are the 2 major associations; however, in many cases a cause for this gastric inflammatory pattern is not identified. <h3>Methodology</h3> Cases of LG were retrieved by a word search (‘lymphocytic gastritis') from the database of Sullivan Nicolaides Pathology for 5 consecutive calendar years (1/1/2004–31/12/2008 inclusive). CD related cases required abnormal small intestinal biopsy and/or positive serology (increased tissue transglutaminase or positive anti-endomysial antibody). HP related cases required positive identification of organisms on the histological sections (usually aided by histochemical or immunohistochemical stains) and/or positive serology and/or positive urease breath test. LG cases without these features were considered non-CD/non-HP related. <h3>Results</h3> 279 cases of LG were identified. The male to female ratio was 1:1 and the age range was 1–87 years. The median age was 55 years. 31.90% had LG associated with HP. 19.71% were associated with CD and 1.79% had evidence of both HP and CD. 130 cases of LG (46.59% of the total) were not associated with CD or current HP infection. These showed seasonal variation. Of these cases, LG was more commonly diagnosed in autumn (40%) or winter (24%) than summer (17%) or spring (19%). As expected, no seasonal variability was observed with CD or HP related cases. <h3>Discussion</h3> Seasonal variability has previously been noted with lymphocytic colitis and duodenal intraepithelial lymphocytosis. An infective aetiology has been proposed to explain this, although no organism/s has been identified. We have been unable to explain this seasonal effect on our non-HP/non-CD associated LG cases.

Cystic fibrosis is a risk factor for celiac disease.

The coexistence of cystic fibrosis (CF) and celiac disease (CD) has been reported. To our knowledge there is no study directly comparing the incidence of CD in CF patients to that in the general population at the same time. There is no published data on genetic predisposition to CD in CF patients either. Therefore, in the present study we aimed to assess the genetic predisposition to CD and its incidence in CF patients comparing it to data from the general population. Two hundred eighty-two CF patients were enrolled in the study. In 230 CF patients the genetic predisposition to CD (the presence of HLA-DQ2/ DQ8) was assessed. In all CF patients, serological screening for CD was conducted. In patients with positive antiendomysial antibodies (EMA) gastroduenoscopy was offered. Intestinal histology was classified according to modified Marsh criteria. The results of serological CD screening in 3235 Polish schoolchildren and HLA-DQ typing in 200 healthy subjects (HS) were used for comparison. Positive EMA was found in 2.84% of the studied CF patients. The incidence of proven CD was 2.13%. The incidence of CD as well as positive serological screening were significantly more frequent in the CF group than in the general population. The frequency of CD-related HLA-DQ alleles in CF and HS did not differ. Genetic predisposition to celiac disease in cystic fibrosis patients is similar to that of the general population. However, our results suggest that cystic fibrosis is a risk factor for celiac disease development.

Coeliac sprue-associated membranoproliferative glomerulonephritis (MPGN)

Coeliac sprue (CS) may occur in association with immune complex-mediated diseases, including IgA nephropathy, dermatitis herpetiformis and thyroiditis. An association of CS with membranoproliferative glomerulonephritis (MPGN) type 1 is rare, with only two prior cases reported. Here we describe a 45-year-old man with no prior medical history who presented initially with microhaematuria, subnephrotic proteinuria and hypocomplementaemia. A renal biopsy revealed MPGN type 1 with negative serologic workup for secondary causes. The patient was treated conservatively with angiotensin-converting enzyme inhibitors. Several months later, he developed daily non-bloody diarrhoea and was found to have worsening hypoalbuminaemia, hypophosphataemia and severe iron deficiency anaemia. A diagnosis of CS was established based on elevated tTGA (IgA anti-tissue transglutaminase) antibody and positive IgA antiendomysial antibody titres. Proteinuria resolved completely following the initiation of a gluten-free diet, without the use of immunosuppressive therapy and despite tapering of angiotensin-converting enzyme inhibitor. This case illustrates that CS-associated MPGN may precede overt clinical evidence of coeliac disease and may respond to gluten-free diet, without resort to immunosuppressive therapy.

Prevalence of Celiac Disease Among Patients with Behcet’s Disease in Iran

Behcet's disease and Celiac disease, both common in Iran, share many immunopathogenic and clinical features. Based on the possible association between these two diseases, this study is designed to determine the frequency of non-diagnosed celiac disease in patients with Behcet's disease. The sera of 288 consecutive patients with Behcet's disease were screened with anti-endomysial antibody and anti-tissue transglutaminase antibody for celiac disease. Those with a positive test underwent upper gastrointestinal endoscopy and duodenal biopsies to confirm the diagnosis of celiac disease. The patients with celiac disease were put on a gluten free diet to evaluate its efficacy on the improvement of their lesions. Fourteen patients had positive anti-tissue transglutaminase antibody test (two with positive anti-endomysial antibody as well). Duodenal biopsies showed findings compatible with Marsh 3 in one and Marsh 1 in three other patients. All the diagnosed patients with celiac disease responded to the gluten free diet. Our findings didn't support any association between celiac disease and Behcet's disease in Iranian patients compared to the general population of Iran.

Celiac Disease and Non-organ-specific Autoantibodies in Patients with Chronic Hepatitis C Virus Infection

Considering that celiac disease (CD) is an autoimmune-based entity and the hepatitis C virus is suspected of being able to trigging autoimmune reactions, it has been hypothesized that hepatitis C virus infection might predispose to CD. The aim of this study was to investigate CD-related antibodies in a large series of hepatitis C virus-infected subjects that were also tested for non-organ-specific autoantibodies (NOSA) as indirect marker of autoimmune disorders. Two hundred and forty-four patients with chronic hepatitis C virus infection (HCV-patients) and 121 patients with HCV-negative liver disease (non-HCV-patients) underwent NOSA determination and celiac serology (firstly, anti-tissue transglutaminase antibodies, then the cases which tested positive were subsequently evaluated for the presence of antiendomysial antibodies). Serum samples from 42 of the HCV-patients who underwent interferon-alpha therapy after enrollment were tested for celiac antibodies and NOSA even after stopping treatment. Additionally, sera from 1,230 blood donors were assayed for celiac serology as healthy control population. Positive anti-endomysial antibodies (AEA) were found in 5/244 (2%) HCV-patients, 1/121 (0.8%) non-HCV-patients and 2/1,230 (0.16%) blood donors, with a significant difference between HCV-patients and blood donors (P = 0.02; Odds ratio 12.8; 95% Confidence Interval 2.4-66). NOSA were found in 51 HCV-patients but only one of them had positive AEA. Eight out of 42 HCV-patients treated with interferon-alpha developed NOSA under therapy and none of them had CD antibodies. AEA occur in 2% of HCV-patients and their presence is independent of other patterns of autoimmunity.

The association between coeliac disease and cardiovascular disease

Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear. To investigate whether coeliac disease patients have an increased risk of cardiovascular events. A community-based cohort study using a record-linkage database. Three hundred and sixty-seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study. The crude rates of cardiovascular events were 9.5 per 1000 person-years (95% CI: 4.4-14.6) in the coeliac cohort and 8.9 per 1000 person-years (95% CI: 7.6-10.3) in the antiendomysial antibody-negative cohort. Compared with the antiendomysial antibody-negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00-3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22-5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort (P = 0.05), and 34% and 26% for the antiendomysial antibody-negative cohort (P < 0.01). Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.

Prevalence of IgA-antiendomysial antibody in a patient cohort with idiopathic low bone mineral density

To investigate the frequency of serum IgA-antiendomysial antibody positivity in patients with low bone mineral density and to assess the risk group for screening of celiac disease. One hundred and thirty-five patients (14 male, 121 female) with idiopathic low bone mineral density were evaluated. The median age was 57.2 years (24-81). Antiendomysial antibody was determined by the immunofluorescence method using a commercial kit (INOVA Diagnostics Inc., CA, USA), which employs a 5 microm thin cryostat section of monkey esophagus as a substrate. Of the 135 patients evaluated, 13 were found to have positive IgA antiendomysial antibody test (9.6%) response. None of the patients had IgA deficiency. Endoscopic appearance and histological examination were normal in all of these patients. Seropositive patients had significantly lower age (48.9 +/- 4.3 vs 59.2 +/- 6.2, P < 0.05), higher ratio of male gender (61.5% vs 4.9%, P < 0.01) and pre-menopausal status (8.7% vs 1.3%, P < 0.01). Lumbar spine and femoral neck z-scores, but not t-scores were significantly lower in seropositive patients. Seropositive patients had lower serum 25 (OH) vitamin D, calcium and higher serum parathormone levels than seronegative patients. The screening of celiac disease in idiopathic osteoporosis should be restricted to patients without classical risk factors (younger, pre-menopausal, male gender) for osteoporosis. Bone mineral density measurements using z-scores should be considered for identifying risk groups for celiac disease.

Celiac disease: Association with adult-onset &lt;i&gt;Still's disease&lt;/i&gt;: Apropos of a clinical case

Adult-onset Still's disease (AOSD) is a rheumatic disorder of unknown etiology characterized by a triad of fever, polyarthritis and evanescent rash. We present a case report of a 28-year-old female who presented with complaints of fever, joint pains, rash, weakness for the past 4 years and diarrhea for the past 2 years. On investigation the patient was diagnosed to be a case of AOSD. Duodenal biopsy report was suggestive of celiac disease with a positive IgA tissue transglutaminase and anti-endomysial antibody. The patient was started on weekly methotrexate and gluten-free diet and her symptoms gradually improved. The patient remains in our follow-up and is doing well.

Celiac disease revealed by diffuse alveolar hemorrhage and heart block

Summary Background Celiac disease is a common disorder characterised by an immune response to ingested wheat gluten. It may be associated with pulmonary or cardiac manifestations. Methods Case report. Results A 52-year old woman with a history of chronic anemia presented with diffuse alveolar hemorrhage and atrioventricular heart block. The diagnosis of celiac disease was based on positive anti-transglutaminase, anti-endomysial, and anti-gliadin antibodies, and on jejunal biopsies showing complete villous atrophy. Conclusion Screening for celiac disease using anti-transglutaminase antibodies should be performed in patients with diffuse alveolar hemorrhage. Electrocardiogram is warranted in patients with celiac disease or alveolar hemorrhage.

Celiac Disease Serology in Irritable Bowel Syndrome and Dyspepsia: A Population-Based Case-Control Study

To determine whether undiagnosed celiac disease is associated with irritable bowel syndrome (IBS) or dyspepsia in the community. A self-report bowel disease questionnaire was mailed to a random sample of Olmsted County, Minnesota, residents aged 20 to 50 years. All respondents who reported symptoms of dyspepsia or IBS (cases) and all respondents without notable gastrointestinal symptoms (controls) were invited to participate (260 eligible subjects; 150 [58%] were studied). Each respondent was examined by a physician, and the medical records of each were reviewed (3 subjects did not meet the criteria for dyspepsia or IBS at the time of the physician interview). Serum was obtained to measure antiendomysial antibodies and tissue transglutaminase (TTg) IgA antibodies using validated assays. A total of 34 subjects had dyspepsia (20 had ulcerlike dyspepsia), 50 had IBS (19 had diarrhea-predominant IBS), and 15 met criteria for both dyspepsia and IBS; 78 were asymptomatic healthy controls. The overall prevalence of positive TTg serology was 4% (95% confidence interval [CI], 1.5%-8.5%). The number of subjects who were seropositive for TTg was 2 of 34 (5.9%) with dyspepsia (95% CI, 0.7%-19.7%), 2 of 50 (4.0%) with IBS (95% CI, 0.5%-13.7%), and 2 of 78 (2.6%) of asymptomatic controls (95% CI, 03%-9.0%) (P = .64 IBS vs controls; P = .58 dyspepsia vs controls). No subjects had positive antiendomysial antibodies. In this community, celiac disease did not explain the presence of either IBS or dyspepsia.

Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal?

Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.

Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture

Objectives The aim of this study was to determine the specificity of increase in intraepithelial lymphocytes (IELs) with normal villous architecture in small bowel biopsy samples for diagnosis of gluten sensitivity (GS) and its significance in the absence of GS. Methods Small bowel biopsy samples from 43 patients with increased IELs and no other pathology were reviewed. Patients with prior diagnosis of GS were excluded. A group of 46 patients with normal duodenal biopsy during the same period served as controls. The clinical records of patients and controls were examined for presenting symptoms, laboratory tests, and final clinicopathological diagnosis. Immunohistochemical characterization of IELs was performed in 13 cases. Results Four (9.3%) patients had GS based on positive IgA antiendomysial antibodies (n = 3) and favorable response to gluten-free diet (n = 4). One patient (2.2%) had partially treated tropical sprue; six patients (14%) had disorders of immune regulation including Hashimoto's thyroiditis (n = 2) and one case each of Graves' disease, rheumatoid arthritis, psoriasis, and multiple sclerosis; and six patients (14%) were on nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, none of the control subjects had GS ( p = 0.05), tropical sprue, or immunoregulatory disorders ( p = 0.011), and one (2.2%) was on NSAIDs ( p = 0.04). Increased IELs were also observed in Crohn's disease, lymphocytic/collagenous colitis, and bacterial overgrowth, but the association did not reach statistical significance. Histological features (number and distribution of IELs, crypt mitoses) and immunophenotypic analysis of IELs did not reliably distinguish GS-related from non–GS-related causes of increased IELs. Conclusions Intraepithelial lymphocytosis in an otherwise normal small bowel biopsy is somewhat nonspecific, but in nearly 10% of cases can be the initial presentation of GS. Therefore all patients with this finding should be investigated for GS. Increased IELs may also be associated with autoimmune disorders and NSAIDs.