Biopsy-proven Celiac Disease Research Articles

Celiac Disease in Children, Adolescents, and Young Adults with Autoimmune Thyroid Disease

To determine the prevalence of antibodies associated with celiac disease and biopsy-proven celiac disease in children with autoimmune thyroid disease. A total of 302 patients with positive anti-thyroid antibodies were prospectively studied. Total immunoglobulin A (IgA) and tissue transglutaminase-IgA (tTG-IgA) levels were obtained. Those with a positive tTG-IgA titer were offered biopsy for definitive diagnosis of celiac disease. A total of 4.6% of subjects with autoimmune thyroid disease had positive tTG-IgA titers. The prevalence of biopsy-confirmed celiac disease was 2.3%. Our population was enriched with patients with type 1 diabetes mellitus (4.3%) and Down syndrome (3.4%). Excluding individuals with these co-morbidities, the prevalence of celiac disease in autoimmune thyroid disease is 1.3%, similar to that of the general population. The positive predictive value of biopsy-proven celiac disease in patients with autoimmune thyroid disease and positive tTG-IgA titer was 54%. The increase in prevalence of celiac disease in autoimmune thyroid disease in our study was largely caused by enrichment with co-morbidities. Without comorbidities or symptoms, screening for celiac disease may not be justified in this population. The specificity of tTG-IgA titer for the diagnosis of celiac disease was decreased in patients with autoimmune thyroid disease compared with the general population.

Psychological stress and coeliac disease in childhood: a cohort study

BackgroundPsychological stress has previously been associated with several immunological diseases, e.g. inflammatory bowel disease. Through questionnaire data from the ABIS study (All Babies In southeast Sweden) we examined the association between psychological stress in the family and biopsy-proven coeliac disease (CD) in the child.MethodsWe used serious life event, parenting stress, and parental worries as measures of psychological stress. Data were collected when the child was 1 and 2.5 years old in some 11,000 and 8,800 children, respectively. CD was confirmed through small intestinal biopsy (with villous atrophy), and the diagnosis was validated through patient chart data.ResultsSerious life event in the family in the child's first 1 or 2.5 years after childbirth was not associated with future CD in the child (Odds Ratio (OR) = 0.45; 95% Confidence Interval (CI) = 0.01-2.65; P = 0.72; and OR = 1.21; 95% CI = 0.43-3.05; P = 0.64, respectively). Neither did we see any association between CD and parenting stress at age 1 year and at 2.5 years (OR = 0.40; 95% CI = 0.01-2.38; P = 0.73 and OR = 0.74; 95% CI = 0.01-4.56; P = 1.00, respectively). Among children exposed to parental worries at 2.5 years, no child had a diagnosis of CD before end of follow-up, compared to 25/8082 (0.3%) among non-exposed children (OR = 0.00; 95% CI = 0.00-2.34; P = 0.64). There was no association between the combined measures of stress and CD.ConclusionThis study found no association between psychological stress and later development of CD in Swedish children. However, we cannot rule out that the lack of such an association is due to limited statistical power.

Screening for celiac disease among patients with Turner syndrome in Brasília, DF, midwest region of Brazil

Several studies have demonstrated a higher prevalence of celiac disease (CD) among females with Turner syndrome when compared to the general population. Nevertheless, there is no record in literature concerning this investigation among Brazilian patients. To assess the prevalence of CD among a group of Brazilian patients with Turner syndrome. Fifty-six females with Turner syndrome and on gluten-containing diet were screened for CD utilizing immunoglobulin A antiendomysium (IgA-EMA) and immunoglobulin A anti-tissue transglutaminase (IgA-tTG) antibody assays. Additionally, they were genotyped for CD human leukocyte antigen (CD-HLA) predisposing alleles. Patients showing positivity in serological testing were offered to perform small intestine biopsy for histological confirmation. Mean age at diagnosis of Turner syndrome was 5.5 ± 4.4 years; mean age at screening for CD was 17.0 ± 9.3 years (from 10 months of age to 52 years). Two girls were positive for IgA-EMA and IgA-tTG, presented predisposing HLA-DQ2 alleles and both had the diagnosis of CD confirmed by jejunal biopsy. The 3.6% prevalence of biopsy-proven CD among this group of females with Turner syndrome is 10 times higher than the one among females from the general population of the same geographical area. This result provides additional support to an association between these two disorders and restates that girls and women with Turner syndrome represent a high risk population for developing CD.

Immune Phenotype of Children with Newly Diagnosed and Gluten-Free Diet-Treated Celiac Disease

Recent data suggest the involvement of both the adaptive and the innate immune system in celiac disease (CD). However, little is known about the immune phenotype of children with CD and its alteration upon dietary intervention. We characterized the prevalence of major interacting members of the adaptive and innate immune system in peripheral blood of newly diagnosed children with CD and tested its alteration with the improvement of clinical signs after the introduction of gluten-free diet (GFD). Peripheral blood was taken from ten children with biopsy-proven CD at the time of diagnosis and after the resolution of clinical symptoms following GFD. As controls, 15 children with functional abdominal pain were enrolled. The prevalence of the cells of adaptive and innate immunity was measured with labeled antibodies against surface markers and intracellular FoxP3 using a flow cytometer. Patients with CD were found to have lower T helper, Th1 and natural killer (NK), NKT and invariant NKT cell prevalence and with higher prevalence of activated CD4(+) cells, myeloid dendritic cells (DC) and Toll-like receptor (TLR) 2 and TLR-4 positive DCs and monocytes compared to controls. After resolution of symptoms on GFD, the majority of these changes normalized, although the prevalence of NK and NKT cell, DC and TLR-2 expressing DCs and monocytes remained abnormal. The immune phenotype in childhood CD indicates the implication of both adaptive and innate immune system. The normalization of immune abnormalities occurs on GFD, but the kinetics of this process probably differs among different cell types.

Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia

The association between celiac disease (CD) and type 1 diabetes mellitus (T1DM) is well known. Up to now, CD prevalence in children and adolescents with T1DM in Serbia has not been reported. The aim of the present study was to determine CD prevalence and its clinical manifestations in patients with T1DM. One hundred and twenty-one patients (70 girls, 51 boys; mean age, 10.8 years) with T1DM (mean duration of diabetes, 3.4 years) and 125 control group participants (75 girls, 50 boys; mean age, 10.4 years) were tested for CD on tissue transglutaminase antibodies (tTG). In seven serologically positive T1DM patients endoscopic small bowel biopsies were taken and examined on histopathology. In all patients with CD and T1DM age, duration of T1DM, height for age, body mass index, glycosylated hemoglobin and clinical symptoms were noted. Nine patients with T1DM were positive on IgA tTG antibodies. In seven of them small bowel biopsy was performed, and all were proven to have CD on histopathology. The prevalence of biopsy-proven CD in children and adolescents with T1DM was significantly higher in the study group compared to controls (5.79%. vs 0.8%, P < 0.05). The significantly higher prevalence of CD in children with type 1 diabetes, in accordance with the large volume of data published in the literature, underlines the need for yearly screening of CD in patients with diabetes in order to promptly start a gluten-free diet when appropriate.

Psychosocial Factors Are More Important Than Disease Activity in Determining Gastrointestinal Symptoms and Health Status in Adults at a Celiac Disease Referral Center

The relative effects of clinical and psychosocial variables on outcome in celiac disease (CD) has not previously been reported. In adult patients with (CD), we studied the relationships among demographics, psychosocial factors, and disease activity with health-related quality of life (HRQOL), health care utilization, and symptoms. Among 101 adults newly referred to a tertiary care center with biopsy-proven CD we assessed: (a) demographic factors and diet status; (b) disease measures (Marsh score, tissue transglutaminase antibody (tTG) level, weight change and additional blood studies); and (c) Psychosocial status (psychological distress, life stress, abuse history, and coping). Multivariate analyses were performed to predict HRQOL, daily function, self-reported health, number of physician visits, and GI symptoms (pain and diarrhea). Impaired HRQOL and daily function was associated with psychological distress and poorer coping. Self-report of poorer health was associated with poorer coping, longer symptom duration, lower education, and greater weight loss. More physician visits were associated with poorer coping, abnormal tTG levels, and milder Marsh classification. Greater pain scores were seen in those with higher psychological distress and greater weight loss. Finally, diarrhea was associated with greater psychological distress and poorer coping. In patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures.

Celiac Disease: The Endocrine Connection

CD is an immune-mediated enteropathy caused by genetically predisposed individuals eating gluten-containing foods (Catassi et al., 2007; Celiac Working Group et al., 2008; Green & Cellier, 2007; Hill et al., 2005). There are several endocrine disorders that are associated with CD. In many of these cases, CD does not present with the typical gastrointestinal symptoms. Nurses working with children who have endocrine conditions need to consider CD as part of the differential and follow-up care plan. This awareness will facilitate more efficient diagnosis and minimize the risk of conditions associated with untreated CD.

S2030 Circulating Hematopoietic Stem Cells and Dynamics of Intestinal Regeneration Following Gluten-Free Diet in Celiac Patients

Purpose: Celiac crisis is a life-threatening syndrome where celiac disease presents with profuse diarrhea and severe metabolic disturbances. Celiac crisis in adults is believed to be uncommon and is not well documented. However, it is likely that many patients with celiac crisis are not definitively diagnosed. In order to improve awareness and to facilitate diagnosis, we reviewed cases of celiac crisis seen at Beth Israel Deaconess Medical Center in Boston, MA and Mayo Clinic in Rochester, MN. These data were used to identify presenting features, formulate diagnostic criteria for celiac crisis in adults and develop treatment strategies. Methods: We reviewed cases of biopsy proven celiac disease in the last 5 years. Celiac crisis was defined as acute onset or rapid progression of gastrointestinal symptoms attributable to celiac disease requiring hospitalization and/or parenteral nutrition along with at least 2 of the 7 factors listed below: 1.Signs of severe dehydration including hemodynamic instability or orthostasis 2.Neurologic dysfunction 3.Renal dysfunction: creatinine >2.0 4.Metabolic acidosis: pH 10 lbs Results: Twelve patients met the above criteria. Of these, 8 were women and 4 were men. 11 developed celiac crisis prior to diagnosis of celiac disease. IgA tissue transglutaminase titer was available for 11 patients. Of these, one had IgA deficiency, and all of the others had elevated tTG, eight with levels greater than 4 times the normal limits. Biopsies of the duodenum in all patients were consistent with a Marsh 3 score. HLA type was available for 10, of which 9 were positive for DQ2 and 1 for DQ8. Patients presented with severe dehydration, renal dysfunction, and electrolyte disturbances, of which hypocalemia was most common. All patients required hospitalization and intravenous fluids and five required parenteral nutrition. Six patients required corticosteroids. All patients had a rapid clinical response to gluten free diet. Conclusion: Celiac crisis is associated with high morbidity and although rarely described, does occur in adults, often without a clear precipitating factor. Patients presentingwith severe unexplained diarrhea and malabsorption should be tested for celiac disease and treatment with systemic steroids or oral budesonide considered. Nutritional support is often required in the short term but most patients ultimately respond to gluten avoidance. We are hopeful that our delineation of formal diagnostic criteria for celiac crisis will aid in identification and management of these patients.

S2029 Celiac Crisis in Adults: Rare or Just Rarely Recognized

Purpose: Celiac crisis is a life-threatening syndrome where celiac disease presents with profuse diarrhea and severe metabolic disturbances. Celiac crisis in adults is believed to be uncommon and is not well documented. However, it is likely that many patients with celiac crisis are not definitively diagnosed. In order to improve awareness and to facilitate diagnosis, we reviewed cases of celiac crisis seen at Beth Israel Deaconess Medical Center in Boston, MA and Mayo Clinic in Rochester, MN. These data were used to identify presenting features, formulate diagnostic criteria for celiac crisis in adults and develop treatment strategies. Methods: We reviewed cases of biopsy proven celiac disease in the last 5 years. Celiac crisis was defined as acute onset or rapid progression of gastrointestinal symptoms attributable to celiac disease requiring hospitalization and/or parenteral nutrition along with at least 2 of the 7 factors listed below: 1.Signs of severe dehydration including hemodynamic instability or orthostasis 2.Neurologic dysfunction 3.Renal dysfunction: creatinine >2.0 4.Metabolic acidosis: pH 10 lbs Results: Twelve patients met the above criteria. Of these, 8 were women and 4 were men. 11 developed celiac crisis prior to diagnosis of celiac disease. IgA tissue transglutaminase titer was available for 11 patients. Of these, one had IgA deficiency, and all of the others had elevated tTG, eight with levels greater than 4 times the normal limits. Biopsies of the duodenum in all patients were consistent with a Marsh 3 score. HLA type was available for 10, of which 9 were positive for DQ2 and 1 for DQ8. Patients presented with severe dehydration, renal dysfunction, and electrolyte disturbances, of which hypocalemia was most common. All patients required hospitalization and intravenous fluids and five required parenteral nutrition. Six patients required corticosteroids. All patients had a rapid clinical response to gluten free diet. Conclusion: Celiac crisis is associated with high morbidity and although rarely described, does occur in adults, often without a clear precipitating factor. Patients presentingwith severe unexplained diarrhea and malabsorption should be tested for celiac disease and treatment with systemic steroids or oral budesonide considered. Nutritional support is often required in the short term but most patients ultimately respond to gluten avoidance. We are hopeful that our delineation of formal diagnostic criteria for celiac crisis will aid in identification and management of these patients.

Celiac Crisis Is a Rare but Serious Complication of Celiac Disease in Adults

Celiac crisis is a life-threatening syndrome in which patients with celiac disease have profuse diarrhea and severe metabolic disturbances. Celiac crisis is rare among adults and not well documented. To improve awareness of this condition and to facilitate diagnosis, we reviewed cases of celiac crisis to identify presenting features, formulate diagnostic criteria, and develop treatment strategies. Cases of biopsy-proven celiac disease were reviewed. Celiac crisis was defined as acute onset or rapid progression of gastrointestinal symptoms that could be attributed to celiac disease and required hospitalization and/or parenteral nutrition, along with signs or symptoms of dehydration or malnutrition. Twelve patients met preset criteria for celiac crisis; 11 developed celiac crisis before they were diagnosed with celiac disease. Eleven patients had increased titres of transglutaminase antibodies and 1 had immunoglobulin A deficiency. Results of biopsy analyses of duodenum samples from all patients were consistent with a Marsh 3 score (33% with total villous atrophy). Patients presented with severe dehydration, renal dysfunction, and electrolyte disturbances. All patients required hospitalization and intravenous fluids, 6 required corticosteroids, and 5 required parenteral nutrition. All patients eventually had a full response to a gluten-free diet. Celiac crisis has a high morbidity and, although rarely described, occurs in adults and often has a clear precipitating factor. Patients who present with severe unexplained diarrhea and malabsorption should be tested for celiac disease; treatment with systemic steroids or oral budesonide should be considered. Nutritional support often is required in the short term but most patients ultimately respond to gluten avoidance.

Positive predictive value of serological diagnostic measures in celiac disease

Celiac disease (CD) antibodies, immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG), IgA endomysium antibody (EMA), IgA and IgG anti-gliadin antibodies (IgA and IgG AGA) are first-line diagnostic tools used in selecting patients for duodenal biopsy. The goal of this study was to evaluate the diagnostic quality of serological testing for CD. CD serological tests (IgA and IgG AGA, anti-tTG and EMA) from 11,915 individuals were measured. Data were combined with clinical data and results of duodenal biopsy using a unique Danish personal identification number. The positive predictive value (PPV) varied according to different combinations of positive CD antibodies, being highest when all antibodies were positive (97.6%). The anti-tTG concentration correlated strongly with EMA positivity, number of additional positive antibodies, and higher PPV. A logistic regression model predicted the probability of later biopsy-proven CD in relation to concentrations of IgA AGA and anti-tTG at initial serological screening. The anti-tTG concentration at initial serological CD screening was highly informative in relation to EMA positivity, number of additional CD specific antibodies and PPV. Furthermore, in the high-risk group of patients investigated, the concentrations of anti-tTG and IgA AGA at initial serological screening could accurately predict the probability of future biopsy-proven CD.

Revival of Gliadin Antibodies in the Diagnostic Work-up of Celiac Disease

Revival of Gliadin Antibodies in the Diagnostic Work-up of Celiac Disease

Prevalence of Celiac disease in Turkish children with type 1 Diabetes Mellitus and their non-diabetic first-degree relatives

The objective of this study was to determine the prevalence of Celiac disease in Turkish children with type 1 Diabetes Mellitus and their non-diabetic first-degree relatives. Forty-eight children with type 1 Diabetes Mellitus (18 males, 30 females; age range: 3.5 to 23 years; mean age: 12.09 +/- 4.78 years), 29 non-diabetic siblings, 40 non-diabetic parents, and 103 healthy children were screened for celiac disease using the IgA and IgG anti-tissue transglutaminase antibody and total serum IgA. Small intestinal biopsy was offered to all antibody-positive patients. Eight of 48 diabetic patients had positive anti-tissue transglutaminase IgA. Selective IgA deficiency was detected in 2 diabetic children and both were positive to anti-tissue transglutaminase IgG. Intestinal biopsy was accepted by 8 of 10 (80%) diabetic children with positive celiac serology. Pathologic examination showed total villous atrophy in 3 (6.3%) diabetic children. Positive anti-tissue transglutaminase IgA was found in 1/29 siblings and 2/40 parents. Celiac disease was confirmed by biopsy in the sibling. Two parents refused the biopsy. The frequency of biopsy-proven celiac disease was found as 1.4 in relatives of diabetic children. None of the serum samples of healthy children comprising the control group showed selective IgA deficiency or positivity for anti-tissue transglutaminase IgA antibody. These findings indicate that the prevalence of celiac disease in Turkish children with type 1 diabetes mellitus is higher than in healthy controls. The 1.4% frequency of Celiac disease in relatives of diabetic children is close to that of controls.

Mucosal Recovery and Mortality in Adults With Celiac Disease After Treatment With a Gluten-Free Diet

Clinical response is typically observed in most adults with celiac disease (CD) after treatment with a gluten-free diet (GFD). The rate of mucosal recovery is less certain. The aims of this study were (1) to estimate the rate of mucosal recovery after GFD in a cohort of adults with CD, and (2) to assess the clinical implications of persistent mucosal damage after GFD. The study group included adults with biopsy-proven CD evaluated at the Mayo Clinic who had duodenal biopsies at diagnosis and at least one follow-up intestinal biopsy to assess mucosal recovery after starting a GFD. The primary outcomes of interest were mucosal recovery and all-cause mortality. Of 381 adults with biopsy-proven CD, 241 (73% women) had both a diagnostic and follow-up biopsy available for re-review. Among these 241, the Kaplan-Meier rate of confirmed mucosal recovery at 2 years following diagnosis was 34% (95% confidence interval (CI): 27-40%), and at 5 years was 66% (95% CI: 58-74%). Most patients (82%) had some clinical response to GFD, but it was not a reliable marker of mucosal recovery (P=0.7). Serological response was associated with confirmed mucosal recovery (P=0.01). Poor compliance to GFD (P<0.01), severe CD defined by diarrhea and weight loss (P<0.001), and total villous atrophy at diagnosis (P<0.001) were strongly associated with persistent mucosal damage. There was a trend toward an association between achievement of mucosal recovery and a reduced rate of all-cause mortality (hazard ratio=0.13, 95% CI: 0.02-1.06, P=0.06), adjusted for gender and age. Mucosal recovery was absent in a substantial portion of adults with CD after treatment with a GFD. There was a borderline significant association between confirmed mucosal recovery (vs. persistent damage) and reduced mortality independent of age and gender. Systematic follow-up with intestinal biopsies may be advisable in patients diagnosed with CD as adults.

Effect of Gluten-Free Diet on Growth and Glycemic Control in Children with Type 1 Diabetes and Asymptomatic Celiac Disease

We aimed to evaluate the effects of a gluten-free diet on growth and glycemic control in children with type 1 diabetes mellitus (DM) and asymptomatic, biopsy-proven celiac disease (CD). Each case of CD was compared to two children with DM and no CD. We studied weight, height, and hemoglobin A1c (HgbAlc) up to 12 months pre- and post- CD diagnosis in 29 cases and 58 controls. The change in body mass index (deltaBMI Z-score) over 2 years was significantly higher in CD cases vs. controls (mean +/- SD 0.33 +/- 0.74 vs. +/- 0.08 +/- 0.46; p = 0.023). However, BMI Z-score did not change in CD patients diagnosed with DM for > 1 year. Mean HgbA1c was similar between groups throughout the study. In conclusion, children with asymptomatic CD and DM do not have significant changes in BMI, height Z-score or metabolic control 1 year post-diagnosis.

The changing frequency of celiac disease diagnosed at the Stollery Children's Hospital.

Celiac disease (CD) is recognized as one of the most common and important autoimmune gastrointestinal disorders affecting children. There is evidence that a diagnosis of CD during childhood improves health outcomes. The increasing prevalence of CD is due to increased awareness of the wide range of extraintestinal symptoms associated with CD. To determine whether there has been a temporal increase in the diagnosis of CD associated with an increased diagnosis of children without typical gastrointestinal symptoms at the Stollery Children's Hospital (Edmonton, Alberta). Patients with biopsy-proven CD diagnosed at the Stollery Children's Hospital from 1998 to 2007, were identified by retrospective chart review. Baseline and follow-up data, including demographics, symptoms, risk factors, anthropometrics and laboratory investigations, were collected. An increase in the frequency of diagnosis of CD was noted during the study period, particularly from January 2003 onward. Before January 2003, nine children were diagnosed with CD - all with typical symptoms. Between January 2003 and January 2007, inclusive, 149 children were diagnosed with CD, of whom 46% had absent or atypical symptoms. At follow-up, 96% of patients reported improved symptoms, including 53% of individuals who reported being asymptomatic before diagnosis. In the last four years of the period studied, the number of children diagnosed with CD at Stollery Children's Hospital increased 11-fold. Screening children at risk for CD, and those with atypical presentations, contributed to the increased number of diagnoses. Identification of CD and establishment of lifelong, dietary gluten avoidance during childhood has important health benefits and should be encouraged.

Neurological symptoms in patients with biopsy proven celiac disease

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 +/- 15 years, mean disease duration 8 +/- 11 years) were recruited through advertisements. All participants adhered to a gluten-free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten-free diet.

Double-Blind Randomized Controlled Trial of Rifaximin for Small Intestinal Bacterial Overgrowth (SIBO) in Celiac Disease

Purpose: Small intestinal bacterial overgrowth (SIBO) is one cause of a poor response to a gluten-free diet and persistent symptoms in celiac disease; a non-controlled trial has reported responses to the oral antibiotic, rifaximin. Methods: This is a single-center, double-blind, randomized controlled trial of 50 patients with biopsy-proven celiac disease and persistent diarrhea, gas, bloating, and abdominal pain despite treatment with a gluten free-diet. They were randomized to placebo (n=25) or treatment with rifaximin 1200mg for 10 days (n=25). An H-lactulose breath test was performed, along with a 15 question survey (the Gastrointestinal Symptom Rating Scale, GSRS) at weeks 0, 2, and 12. Statistical analysis was performed using the chi-square test for categorical data, the two-sample t-test for continuous variables, and the nonparametric Wilcoxon test for GSRS scores. Results: SIBO was seen in 59.1% at initiation of the study and was intermittently present in 12 patients receiving placebo. There was no difference in the baseline prevalence of SIBO between the placebo and treatment groups (52% vs. 68%, p=0.14). Completion of the study was achieved by 21 patients in the placebo group and 20 patients in the treatment group. Drop-outs occurred at weeks 0 (n=1), 2 (n=5), and 12 (n=3). By week 2, the prevalence of SIBO was decreased in the treatment group (63.6% vs. 36.4%, p=0.04), but this response is not sustained by week 12 (66.7% vs. 65%, p=0.91). Normalization of a baseline abnormal breath test was more likely in the treatment group than placebo group, but did not reach significance (40.9% vs. 18.2%, p=0.07). During week 2, patients in the placebo group with baseline abnormal breath tests appeared to have higher GSRS-diarrhea scores (by 1.36 points, p=0.0013) than those with normal breath tests in the placebo group. Otherwise, GSRS scores were unaffected by treatment with rifaximin, regardless of presence of SIBO. Conclusion: SIBO is common in celiac disease with persistent symptoms, despite a gluten-free diet and it may be intermittent. Treatment with rifaximin does not appear to affect patients' reporting of gastrointestinal symptoms, but does produce an initial reduction in abnormal breath test results that is not sustained. A longer, higher dose or intermittent course of treatment may be required for a longstanding response.

A Pilot Study on the Noninvasive Evaluation of Intestinal Damage in Celiac Disease Using I-FABP and L-FABP

In the clinical management of celiac disease, new noninvasive tools for evaluation of intestinal damage are needed for diagnosis and for follow-up of diet effects. Fatty acid binding proteins (FABP) are potentially useful for this purpose as these are small cytosolic proteins present in enterocytes and sensitive markers for intestinal mucosal damage. First, the distribution and microscopic localization of FABP in the healthy human intestine was examined. Second, levels of circulating FABP were measured in patients with celiac disease before and after introducing a gluten-free diet (GFD) and in healthy controls. The distribution and microscopic localization of FABP in normal human intestinal tissue was assessed using surgical intestinal specimens of 39 patients. Circulating levels of intestinal (I)-FABP and liver (L)-FABP were determined in 26 healthy volunteers and 13 patients with biopsy proven celiac disease. Ten of these patients were reevaluated within 1 year after starting GFD. I-FABP and L-FABP are predominantly present in the small intestine, mainly the jejunum. Moreover, FABP are expressed in cells on the upper part of the villi, the initial site of destruction in celiac disease. Circulating levels of FABP are significantly elevated in untreated patients with biopsy proven celiac disease compared with healthy controls (I-FABP: 784.7 pg/mL vs. 172.7 pg/mL, P<0.001; L-FABP: 48.4 ng/mL vs. 10.4 ng/mL, P<0.001). In response to GFD, these concentrations normalize. Results of this pilot study strongly suggest that FABP can be used as a noninvasive method for assessment of intestinal damage in celiac disease. Besides an additional role in the diagnosis of celiac disease, FABP potentially enable noninvasive monitoring of the GFD effects.

A Validated Disease-Specific Symptom Index for Adults With Celiac Disease

Although the incidence of celiac disease (CD) is increasing, studies have been hampered by the lack of validated outcome measures. We sought to create a disease-specific Celiac Symptom Index (CSI) to reliably assess relevant symptoms. A 36-item questionnaire was created after design by an expert committee and review/revision by patient focus groups. The survey, covering domains of CD-related symptoms and general health, was initially administered to 154 individuals with biopsy-proven CD; immunoglobulin (Ig)A tissue transglutaminase titers were determined, and gluten-free diet adherence was evaluated by a dietitian. The questionnaire was then revised to exclude questions with poor test characteristics and administered to a second, independent group of 52 individuals, to ensure validity. The subscales of "specific symptoms" and "general health" had excellent psychometric qualities that consisted of 11 and 5 items, respectively. The additive score based on these items was correlated with current general health, as measured by a visual analog scale and short form 36 general health subscale (P < or = .001 for both), as well as degree of adherence to the gluten-free diet (P = .008), lending external validity to the CSI. The resulting 16 questions make up the first CD-specific symptom index. The CSI allows for disease-specific monitoring of symptoms as an independent outcome measure or as part of a surrogate for disease activity in individuals with CD. The CSI might be an important tool for future clinical CD research.