Quantitative assessment of endoscopic images for degree of villous atrophy in celiac disease.

BACKGROUND: The degree of villous atrophy in celiac disease is difficult to assess at endoscopy. We sought to develop a quantitative technique for the evaluation of villous atrophy in endoscopic images. METHOD: In ten celiac patients as identified by standard endoscopy with biopsy, and ten control patients, standard and videocapsule endoscopic images of the duodenum were digitized. Subimages 7.5 × 7.5 mm(2) in area from random locations within each image were assessed by measuring the length of mucosal fissures per unit area (L), and correlating L with the histologic grade of villous atrophy as determined by modified Marsh criteria. RESULTS: Mean L values for standard endoscopic images were 37.8, 43.3, 64.1, and 83.5 mm for Marsh grades II, IIIa, IIIb, and IIIc, respectively. Mean L values for videocapsule images were 49.1, 50.0, 64.7, and 72.4 mm for Marsh grades II, IIIa, IIIb, and IIIc, respectively. Significant differences in the means existed between celiac images (Marsh scores II-IIIc) versus controls (p < 0.001) for both endoscopic and videocapsule images. There were no significant differences between measurements obtained from endoscopic versus videocapsule images. CONCLUSIONS: Quantified image analysis correlates with the histologic grade of villous atrophy, is automated, and lacks observer bias, thus lending itself to standardization.

Psychosocial factors are more important than disease activity in determining gastrointestinal symptoms and health status in adults at a celiac disease referral center.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: In patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures.

Celiac disease: similar presentations in the elderly and young adults.

BACKGROUND/AIMS: Studies have shown that celiac disease can affect individuals in all age groups. However, few studies have described the disease in the elderly. The goal of this study is to characterize celiac disease in the elderly by comparing to a population of young adults with celiac disease. METHODS: Review of a tertiary center database of patients with celiac disease was performed to identify two groups of patients, an elderly cohort ≥ 65 years and a young adult cohort aged 18-30 years, with biopsy-confirmed celiac disease. Information obtained included symptom duration, clinical presentation, small intestinal pathology, associated conditions, and the presence of bone disease. RESULTS: Included in the study were 149 young adult and 125 elderly patients; the latter represented 12.4% of the patients in our database. The duration of symptoms prior to diagnosis was similar, 5.8 ± 12 years and 6.14 ± 12.6 years in the young adult and elderly cohorts, respectively (p = 0.119). There was no significant difference in the mode of presentation of illness. Diarrhea was the main presenting symptom (49% in young adults vs. 50% in the elderly, p = 0.921). There was a similar prevalence of autoimmune disease (19% in young adults vs. 26% in the elderly, p = 0.133). Thyroid disease and neuropathy were more prevalent in the elderly (p = 0.037 and p = 0.023, respectively). The degree of villous atrophy and prevalence of bone disease were similar in each group. CONCLUSIONS: Surprisingly, the presentation of celiac disease both clinically and histologically is similar in elderly and young adult patients. The factors triggering disease at any given age remain unclear and warrant further study.

Serum cytokine elevations in celiac disease: association with disease presentation.

Celiac disease (CD) is an autoimmune disorder that is triggered by an immune response to gluten in genetically predisposed individuals. Although considered a primary gastrointestinal disease, CD is now known to have widespread systemic manifestations. We attempted to define the nature and role of systemic cytokine levels in the pathophysiology of CD. Multiplex cytokine assays were performed on four different groups of adult patients; patients with active CD (ACD), patients on a gluten-free diet (GFD) with positive TTG IgA antibodies, patients on a GFD with negative antibodies, and those with refractory CD (RCD). The results were compared with values in healthy adult controls. Patients with active CD and those on GFD with positive antibodies had significantly higher levels of proinflammatory cytokines, such as interferon-gamma, interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6 and IL-8, and also T(h)-2 cytokines such as IL-4 and IL-10, compared with normal controls and patients on GFD without antibodies. Interestingly patients on GFD for less than 1 year had significantly higher levels of both proinflammatory cytokines and T(h)2 cytokines compared with the patients on GFD for more than 1 year. In addition, a statistically significant correlation between levels of TTG IgA titers and serum levels of T(h)-2 cytokines IL-4 (p < 0.001), IL-10 (p < 0.001) and inflammatory cytokines such as IL-1alpha (p < 0.001), IL-1beta (p < 0.005), and IL-8 (p < 0.05) was observed.

Comparison of commercially available serologic kits for the detection of celiac disease.

BACKGROUND: The sensitivity and specificity of current antihuman tissue transglutaminase (tTG) IgA assays used to detect celiac disease reportedly approach 100%. In addition, the sensitivity of new generation deamidated gliadin peptide (alpha-DGP) antibody assays has also been reported to be similar to the tTG IgA assays. In routine clinical practice, however, the sensitivities and specificities of these tests for diagnosing celiac disease seem to be lower. AIM: We analyzed sensitivities and specificities of 4 IgA tTG and 3 deamidated gliadin peptide (alpha-DGP) kits. METHODS: The performance of 4 tTG IgA assays, A: Inova (Hu red blood cell), B: Binding site (rHu Ag), C: Eurospital (rHu Ag), D: Immco (rHu Ag) and 3 Inova alpha-DGP assays, E: alpha-DGP-IgA, F: alpha-DGP-IgG, and G: alpha-DGP-IgA+G was evaluated using sera from different subsets of celiac disease patients and controls; group 1: active celiac disease n=28, group 2: gluten-free diet n=54, group 3: healthy controls n=40, group 4: disease controls n=57(Crohn's disease n=17, chronic hepatitis n=40). RESULTS: Using the manufacturer's cut-off values, the sensitivities and specificities of different kits ranged from 71.4% to 96.4% and 87.5% to 100%, respectively. When group 1 was compared with disease controls, sensitivities remained the same but specificities decreased. Receiver operating characteristic plot derived cut-off values modified decision thresholds in all assays except kit (G). Kappa analysis demonstrated variable degrees of agreement. All assays demonstrated higher sensitivities for patients with higher grades of villous atrophy. CONCLUSIONS: Overall sensitivity was at or below 90%, which is lower than that reported in the literature. Performance of the recombinant and red blood cell antigen-based tTG assays was similar, whereas the alpha-DGP assays demonstrated lower values. Receiver operating characteristic plot derived cut-off values altered test results. Many factors affect the results of these tests and clinicians should be aware of their limitations.

Tissue transglutaminase antibodies in individuals with celiac disease bind to thyroid follicles and extracellular matrix and may contribute to thyroid dysfunction.

BACKGROUND: Individuals with active celiac disease (CD+) have an increased incidence of thyroid dysfunction, which improves on a gluten-free diet (CD-). We investigated whether tissue transglutaminase-2 IgA antibodies (anti-TGase II) present in sera of patients with celiac disease react with thyroid tissue and possibly contribute to thyroid disease. METHODS: Serum from 40 active celiac patients taken before a gluten-free diet (CD+), 46 patients on a gluten-free diet (CD-), 40 normal controls (NC), and 25 with Crohn's disease (CROHN) was used. All sera were screened for antithyroperoxidase antibodies (TPO-AB) and thyroglobulin antibodies (TG-AB), and indirect immunofluorescence (IIF) was performed on primate thyroid tissue sections using TPO-AB- and TG-AB-negative sera. RESULTS: IIF with thyroid seronegative, anti-TGase II-positive CD+ sera (n = 23) demonstrated staining of thyroid follicular cells and extracellular matrix, in an identical pattern with monoclonal anti-human TGase II antibody. Evidence of TGase II as the antigen in thyroid tissue was supported by elimination of the IIF pattern when sera were depleted of anti-TGase II by pretreatment with human recombinant TGase II. No staining of thyroid tissue was observed when sera from CD+ patients that were negative for TGase II antibodies, or sera from NC subjects were used. Thyroid antibodies were found in 43% of CD+ patients, significantly higher than NC and CROHN patients (p < 0.0001). In addition, a positive correlation was observed between anti-TGase II and TPO-AB titers (p = 0.0001; r = 0.63). CONCLUSIONS: Anti-TGase II antibodies bind to TGase II in thyroid tissue, and titers correlate with TPO antibody titers. These findings suggest that anti-TGase II antibodies could contribute to the development of thyroid disease in celiac disease.

Chronic hepatitis C virus and celiac disease, is there an association?

Celiac disease (CD) has been epidemiologically associated with chronic hepatitis C (HCV), and CD activation after the initiation of interferon (IFN-alpha) in patients with HCV is documented. However, clear association of CD and HCV is lacking. A prospectively maintained database of 878 CD patients showed a prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and depression prompted the diagnosis of CD during or after IFN-alpha therapy in four cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls and 19 disease controls) were prospectively screened for CD. The mean age of the subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received IFN-alpha therapy (16% at the time of testing for CD). Two HCV patients (1%) had positive tTG-IgA but these had negative endomysial antibody (EMA) and normal duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine screening of CD in HCV patients is not warranted, however, the presence of CD should be considered in the setting of clinical deterioration during or after IFN-alpha therapy.

Extraintestinal manifestations of celiac disease.

Celiac disease is an autoimmune disorder that occurs in genetically predisposed individuals as the result of an immune response to gluten. It is present in approximately 1% of the population. Diarrhea has become a less common mode of presentation (<50% of cases) than it once was. Other presentations include iron-deficiency anemia, osteoporosis, dermatitis herpetiforme, and neurologic disorders, mainly peripheral neuropathy and ataxia. Arthritis is commonly found in patients with celiac disease when systematically sought. Overall, autoimmune diseases occur more frequently (three to ten times more) in those with celiac disease than in the general population. A gluten-free diet is the standard of treatment, although its effect on some of the extraintestinal manifestations remains to be determined.