Suzanne K. Lewis

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.

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.

The development and validation of a new coeliac disease quality of life survey (CD-QOL).

Aliment Pharmacol Ther 31, 666–675

Budesonide in the Treatment of Refractory Celiac Disease

OBJECTIVE:Corticosteroids are used in patients with refractory celiac disease. In order to minimize their systemic side effects, we assessed the role of a locally active sustained release corticosteroid with minimal systemic bioavailability in patients with refractory celiac disease in an open labeled noncontrolled study.METHODS:Patients who received budesonide for refractory celiac disease were classified according to whether they were primarily or secondarily unresponsive to the diet, and whether they had a polyclonal (type I) or clonal (type II) expansion of intraepithelial lymphocytes. The response to budesonide was assessed globally and by reduction in bowel movements.RESULTS:Patients (N = 29, 72% female) received budesonide for a mean of 6.7 ± 8.5 months, 5 patients (18%) had type II disease (clonal T-cell population); 76% responded to the medication, 55% completely. Response occurred when budesonide was used alone or with oral corticosteroids and/or azathioprine. There was an objective improvement in the number of bowel movements in those that responded. Response occurred in those with either primary or secondary refractory disease and in those with type II disease, irrespective of the presence of microscopic colitis (N = 7). There was no improvement in the duodenal biopsy over the study period and there were no side effects of budesonide.CONCLUSIONS:Budesonide may be of value in the management of refractory 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.

Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients

Collagenous sprue is associated with high morbidity; however, the etiology of this disorder is unclear. Data regarding the pathological and clinical manifestations of patients with collagenous sprue are also limited. We, thus, undertook this study to gain insight into the etiology, disease manifestations and outcomes of collagenous sprue. We searched our departmental database (1999–2008) to identify cases of collagenous sprue and to obtain clinical and laboratory data. Small bowel histology, including thickness of subepithelial collagen, intra-epithelial lymphocyte phenotype and results of T-cell clonality assays were evaluated. Nineteen patients (15 women, 4 men, age 22–80 years, mean 57 years) were identified. Seventeen (89%) had celiac disease and two had unclassified sprue; 9 of 17 (53%) celiac disease patients had refractory disease; 5 of 15 (33%) lacked diarrhea (atypical presentation), including 2 of 6 (33%) with active (untreated) celiac disease and 3 of 9 (33%) with refractory celiac disease. Autoimmune disorders were seen in 12 of 19 (63%) patients and microscopic colitis (n=7), lymphocytic gastritis (n=2) or collagenous gastritis (n=2) were seen in nine patients. Subepithelial collagen thickness was mildly (n=6), moderately (n=10), or markedly (n=3) increased and villous atrophy was total (n=13) or subtotal (n=6). Phenotypically aberrant intraepithelial lymphocytes were not detected in any case. Polymerase chain reaction analysis showed a dominant T-cell clone in the only patient with refractory celiac disease type II. Histological improvement occurred in 7 of 11 (64%) patients. Overall, 8 of 19 (42%) responded to gluten-free diet, including 2 of 9 (22%) with refractory celiac disease and 10 responded to immunomodulatory therapy, including 6 of 9 (67%) with refractory celiac disease. Only one patient died from complications of refractory celiac disease. No patient developed lymphoma. The vast majority of our patients with collagenous sprue had celiac disease. Although, many patients required immunomodulatory therapy for symptom control, a subset responded to gluten-free diet alone. In our experience, collagenous sprue patients had relatively good clinical outcomes.

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

BackgroundThe 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.MethodsAmong 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).ResultsImpaired 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.ConclusionsIn patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures.

Celiac Disease in African-Americans

Celiac disease is generally under diagnosed in the United States and it is unclear whether the disease is encountered in ethnic minorities. Our purpose is to describe a case series of African-American patients with celiac disease. Nine (1.3%) African-American patients with celiac disease were identified from a prospectively generated database of 700 patients with biopsy proven celiac disease and seen between 1981 and 2004. Females predominated, with seven, compared to two males. Diarrhea was the presentation in only two patients, while three presented with iron deficiency anemia. One third had at least one autoimmune disease. Compliance with a gluten-free diet, the only medical therapy of this disease, was poor. Only four patients adhered strictly to the diet. Celiac disease occurs in African-Americans and may well be underdiagnosed. Special attention needs to be given to methods that encourage adherence to the diet in minority groups.