Christina A. Tennyson

Villous atrophy and negative celiac serology: a diagnostic and therapeutic dilemma.

OBJECTIVES:Patients with villous atrophy (VA) and negative celiac disease (CD) serologies pose a diagnostic and therapeutic dilemma. When a definitive etiology for VA is not determined, patients are characterized as having unclassified sprue (US), the optimal management of which is unknown.METHODS:We studied adult patients with VA on biopsy and negative celiac serologies, evaluated at our tertiary referral center over a 10-year period. Testing for HLA DQ2/8 alleles, antienterocyte antibodies, giardia stool antigen, bacterial overgrowth, total serum immunoglobulins, and HIV was noted. Treatment, response, and repeat-biopsy findings were recorded.RESULTS:The most common diagnoses of the 72 patients were seronegative CD, medication-related villous atrophy, and US. Of those with US, the majority reported symptomatic improvement with immunosuppressive therapy. Some patients initially labeled as unclassified were found to have VA associated with olmesartan use.CONCLUSIONS:The role of medications in the development of VA and the optimal dose and length of immunosuppression for patients with US should be investigated further.

Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the Continuous National Health and Nutrition Examination Survey 2009–2010

Abstract Objectives. Clinical inference suggests the prevalence of non-celiac gluten sensitivity is substantially higher than that of celiac disease in the USA. Unfortunately, there are currently no data supporting these claims. The authors analyzed nationally representative data to estimate the prevalence of adherence to a gluten-free diet among participants without celiac disease and also to characterize the demographics and general health status of these participants. Study design and setting. The Continuous National Health and Nutrition Examination Survey (NHANES) 2009–2010 enrolled 7762 individuals representing the civilian, non-institutionalized, US population free of celiac disease. Participants responded to interviewer administered questionnaires regarding current adherence to a gluten-free diet. Prevalence estimates were computed using SAS survey procedures. Results. There were 49 individuals who reported current adherence to a gluten-free diet reflecting a weighted prevalence of 0.548% (95% CI 0.206–0.889). The prevalence of a gluten-free diet was higher in females (0.58%) than males (0.37%), although this was not statistically significant (p = 0.34). Participants reporting a gluten-free diet were older (46.6 vs. 40.5 years, p = 0.005), had higher high-density lipoprotein, lower iron and lower body mass index. Conclusions. The estimated national prevalence of non-celiac gluten sensitivity is 0.548%, approximately half that of celiac disease. Future studies are merited in order to better understand the population burden of non-celiac gluten sensitivity.

Prospective study of the role of duodenal bulb biopsies in the diagnosis of celiac disease.

BACKGROUND Studies have demonstrated that villous atrophy in celiac disease is patchy and have suggested that duodenal bulb biopsies aid in diagnosis. OBJECTIVE To determine the role of the addition of duodenal bulb biopsies to distal duodenum (D2) biopsies in the diagnosis of celiac disease. DESIGN Prospective, case-control study. SETTING Tertiary referral hospital. PATIENTS Patients undergoing upper endoscopy with biopsy for diagnosis or follow-up of celiac disease and control patients. INTERVENTIONS Blinded review of duodenal biopsy samples. MAIN OUTCOME MEASUREMENTS Increasing the yield as well as accuracy of the histologic diagnosis of celiac disease with the addition of bulb biopsies. RESULTS Of 128 patients enrolled in the study, 67 had celiac disease. Of 1079 biopsy specimens, only 319 (30%) were adequate for complete histologic analysis, resulting in 40 celiac patients and 40 control patients for analysis. Of the 40 celiac patients, 35 (87.5%) had atrophy in either the bulb or D2, 30 (75%) exhibited atrophy at both sites with an identical grade of atrophy seen in 18 patients (45%). Fourteen patients (35%) had identical types of Marsh lesions in both biopsy sites. Twelve patients (30%) had atrophy detected in the bulb, D2, or both, but lacked intraepithelial lymphocytes and thus could not be assigned a Marsh grade. Five patients (13%) had a diagnosis of celiac disease based on findings in the bulb biopsy only. LIMITATIONS Small sample size and study performed in an academic medical center. CONCLUSIONS Our study confirms the patchy nature of villous atrophy as well as intraepithelial lymphocytosis in biopsy specimens from individuals with celiac disease. Adding duodenal bulb biopsies to our sampling regimen increased the diagnostic yield of celiac disease.

Distinguishing patients with celiac disease by quantitative analysis of videocapsule endoscopy images

BACKGROUND Although videocapsule endoscopy images are helpful in the evaluation of celiac disease, their interpretation is subjective. Quantitative disease markers could assist in determining the extent of villous atrophy and response to treatment. METHOD Capsule endoscopy images were acquired from celiac patients with small bowel pathology (N=11) and from control patients (N=10). Image resolution was 576x576 pixels in dimension, 256 grayscale levels, and had a 2 s(-1) frame rate. Pixel brightness and image texture were measured over 10x10 pixel subimages and then averaged for 56x56 subimages per frame. Measurements were obtained at five locations from proximal to distal small intestine in each patient. At each location, measurements were calculated using 200 consecutive image frames (100s). Mean frame-to-frame pixel brightness, image texture, and periodicity in brightness, an estimate of wall motion or intestinal motility, were computed and used for classification with a nonlinear discriminant function. RESULTS From pooled data, celiac images had greater texture than did images from control patients (p<0.001) and exhibited more frame-to-frame brightness variation as well (p=0.032). The dominant period of brightness was longer in celiacs (p=0.001), possibly indicating decreased motility. Using the markers for three-dimensional nonlinear classification of celiacs versus controls, sensitivity was 92.7% and specificity was 93.5%. The relationship between dominant period and small intestinal transit time was approximately linear for both celiacs and controls (r(2)=0.42 and r(2)=0.55, respectively). CONCLUSIONS Videocapsule images can be quantified to detect villous atrophy throughout the small intestine, and to distinguish individuals with celiac disease from individuals lacking mucosal atrophy.

Variability in small bowel histopathology reporting between different pathology practice settings: impact on the diagnosis of coeliac disease

Background and Aims Coeliac disease (CD) diagnosis requires the detection of characteristic histological alterations of small bowel mucosa, which are prone to interobserver variability. This study evaluated the agreement in biopsy interpretation between different pathology practice types. Methods Biopsies from community hospitals (n=46), university hospitals (n=18) and commercial laboratories (n=38) were blindly assessed by a pathologist at our institution for differences in histopathology reporting and agreement in diagnosis of CD and degree of villous atrophy (VA) by κ analysis. Results Agreement for primary diagnosis was very good between this institution and university hospitals (κ=0.888), but moderate compared with community hospitals (κ=0.465) or commercial laboratories (κ=0.419). Diagnosis differed in 26 (25%) cases, leading to a 20% increase in CD diagnosis after review. Among those diagnosed with CD by both institutions (n=49), agreement in degree of VA was fair (κ=0.292), with moderate agreement between the authors and commercial laboratories (κ=0.500) and fair with university hospitals (κ=0.290) or community hospitals (κ=0.211). The degree of VA was upgraded in 27% and downgraded in 2%. Within different Marsh score categories, agreement was poor (κ<0.0316) for scores 1 and 2, both missed at other centres, and fair or moderate for scores 3a and 3b. Information regarding degree of VA and intraepithelial lymphocytosis was lacking in 26% and 86% of reports and non-quantifiable descriptors, eg, ‘blunting’ or ‘marked atrophy’ were prevalent. Conclusions CD-related histological changes are underdiagnosed in community-based hospitals and commercial pathology laboratories. Because incorrect biopsy interpretation can cause underdiagnosis of CD, greater CD awareness and uniformity in small bowel biopsy reporting is required among pathologists.

Prevalence of Migraine in Patients With Celiac Disease and Inflammatory Bowel Disease

Objective.— To assess the prevalence of headache in clinic and support group patients with celiac disease and inflammatory bowel disease (IBD) compared with a sample of healthy controls.

Sex and racial disparities in duodenal biopsy to evaluate for celiac disease

BACKGROUND Celiac disease (CD) is common but underdiagnosed in the United States. Serological screening studies indicate that, although CD occurs at the same frequency in both sexes, women are diagnosed more frequently than men (2:1). CD is less frequently diagnosed among black patients, though the seroprevalence in this group is not known. OBJECTIVE To measure the rates of duodenal biopsy during EGD for symptoms consistent with CD. DESIGN Retrospective cohort study. SETTING Clinical Outcomes Research Initiative National Endoscopy Database, spanning the years 2004 through 2009. PATIENTS Adults undergoing EGD for the indication of diarrhea, anemia, iron deficiency, or weight loss, in which the endoscopic appearance of the upper GI tract was normal. MAIN OUTCOME MEASUREMENT Performance of duodenal biopsy. RESULTS Of 13,091 individuals (58% female patients, 9% black patients) who met the inclusion criteria, duodenal biopsy was performed in 43%, 45% of female patients and 39% of male patients (P < .0001). Black patients underwent duodenal biopsy in 28% of EGDs performed compared with 44% for white patients (P < .0001). On multivariate analysis, male sex (odds ratio [OR] 0.81; 95% CI, 0.75-0.88), older age (OR for 70 years and older compared with 20-49 years, 0.51; 95% CI, 0.46-0.57), and black patients (OR 0.55; 95% CI, 0.48-0.64) were associated with decreased odds of duodenal biopsy. LIMITATIONS Lack of histopathologic correlation with CD prevalence. CONCLUSIONS In this multiregional endoscopy database spanning the period from 2004 through 2009, rates of duodenal biopsy increased modestly over time, but overall remained low in patients with possible clinical indications for biopsy. Nonperformance of duodenal biopsy during endoscopy may be contributing to the underdiagnosis of CD in the United States.

Interest in medical therapy for celiac disease

Objectives: A gluten-free diet is the treatment for celiac disease, but pharmaceutical agents are being developed. The level of interest amongst patients in using a medication to treat celiac disease is unknown. This study examined the level of interest amongst patients in medication to treat celiac disease. Methods: A questionnaire was distributed to celiac disease patients and data were collected on demographics, presentation, and interest in medication. Three validated celiac disease-specific instruments were incorporated: Celiac Disease Associated Quality of Life, the Celiac Symptom Index, and the Celiac Dietary Adherence Test. Results: Responses were received from 365 individuals with biopsy-proven celiac disease. Respondents were 78% (n = 276) female, 48% (n = 170) over 50 years of age, and experienced a classical (diarrhea predominant) presentation in 44% (n = 154). Of the 339 individuals answering the question regarding use of a medication to treat celiac disease, 66% were interested. Interest was greatest in older individuals (71% >50 years of age versus 60% <50 years of age, p = 0.0415), men (78% men versus 62% women, p = 0.0083), frequent restaurant customers (76% versus 58%, p = 0.0006), those dissatisfied with their weight (73% versus 51%, p = 0.0003) and those concerned with the cost of a gluten-free diet (77% versus 64%, p = 0.0176). Length of time since diagnosis, education, presentation, and symptoms with gluten exposure did not demonstrate any effect. Interest in medication was associated with a worse quality of life (CD-QOL 69.4 versus 80.1, p < 0.0001). Conclusions: Most individuals with celiac disease are interested in using a medication. Interest was highest among men, older individuals, frequent restaurant customers, individuals dissatisfied with their weight or concerned with the cost of a gluten-free diet, and those with a worse quality of life.

Implementation of a polling protocol for predicting celiac disease in videocapsule analysis

AIM To investigate the presence of small intestinal villous atrophy in celiac disease patients from quantitative analysis of videocapsule image sequences. METHODS Nine celiac patient data with biopsy-proven villous atrophy and seven control patient data lacking villous atrophy were used for analysis. Celiacs had biopsy-proven disease with scores of Marsh II-IIIC except in the case of one hemophiliac patient. At four small intestinal levels (duodenal bulb, distal duodenum, jejunum, and ileum), video clips of length 200 frames (100 s) were analyzed. Twenty-four measurements were used for image characterization. These measurements were determined by quantitatively processing the videocapsule images via techniques for texture analysis, motility estimation, volumetric reconstruction using shape-from-shading principles, and image transformation. Each automated measurement method, or automaton, was polled as to whether or not villous atrophy was present in the small intestine, indicating celiac disease. Each automatons vote was determined based upon an optimized parameter threshold level, with the threshold levels being determined from prior data. A prediction of villous atrophy was made if it received the majority of votes (≥ 13), while no prediction was made for tie votes (12-12). Thus each set of images was classified as being from either a celiac disease patient or from a control patient. RESULTS Separated by intestinal level, the overall sensitivity of automata polling for predicting villous atrophy and hence celiac disease was 83.9%, while the specificity was 92.9%, and the overall accuracy of automata-based polling was 88.1%. The method of image transformation yielded the highest sensitivity at 93.8%, while the method of texture analysis using subbands had the highest specificity at 76.0%. Similar results of prediction were observed at all four small intestinal locations, but there were more tie votes at location 4 (ileum). Incorrect prediction which reduced sensitivity occurred for two celiac patients with Marsh type II pattern, which is characterized by crypt hyperplasia, but normal villous architecture. Pooled from all levels, there was a mean of 14.31 ± 3.28 automaton votes for celiac vs 9.67 ± 3.31 automaton votes for control when celiac patient data was analyzed (P < 0.001). Pooled from all levels, there was a mean of 9.71 ± 2.8128 automaton votes for celiac vs 14.32 ± 2.7931 automaton votes for control when control patient data was analyzed (P < 0.001). CONCLUSION Automata-based polling may be useful to indicate presence of mucosal atrophy, indicative of celiac disease, across the entire small bowel, though this must be confirmed in a larger patient set. Since the method is quantitative and automated, it can potentially eliminate observer bias and enable the detection of subtle abnormality in patients lacking a clear diagnosis. Our paradigm was found to be more efficacious at proximal small intestinal locations, which may suggest a greater presence and severity of villous atrophy at proximal as compared with distal locations.

Is Dietitian Use Associated with Celiac Disease Outcomes

A gluten-free diet (GFD) is the treatment for celiac disease (CD), but due to its complexity, dietitian referral is uniformly recommended. We surveyed patients with CD to determine if dietitian use is associated with quality of life, symptom severity, or GFD adherence. The survey utilized three validated CD-specific instruments: the CD quality of life (CD-QOL), CD symptom index (CSI) and CD adherence test (CDAT). Four hundred and thirteen patients with biopsy-proven CD were eligible for inclusion. The majority (77%) were female and mean BMI was 24.1. Over three-quarters of patients (326, 79%) had seen a dietitian, however, 161 (39%) had seen a dietitian only once. Age, sex, and education level were not associated with dietitian use; nor was BMI (24.6 vs. 24.0, p = 0.45). On multivariate analysis, adjusting for age gender, education, duration of disease, and body mass index, dietitian use was not associated with CD-QOL, CSI, or CDAT scores. Our survey did not show an association between dietitian use and symptom severity, adherence, or quality of life. Delay in diagnosis was associated with poorer outcomes. This is a preliminary study with several limitations, and further prospective analysis is needed to evaluate the benefits and cost-effectiveness of dietitian-referral in the care of celiac disease patients.