乳糜泻诊断的研究进展

乳糜泻(CD)是具有遗传易感性的个体因摄入麸质而触发的一种免疫介导的全身性疾病。其特点为小肠(尤其是空肠)黏膜绒毛的萎缩以及营养物质吸收不良,禁食含麸质的食物(小麦、黑麦、大麦)能使症状缓解,再进食可迅速复发。以往认为本病少见,目前世界范围的流行病学资料证实其发病率并不低且逐渐增加。本文就CD诊断的研究进展作一综述。     

Cost-effectiveness Analysis of Strategies for Diagnosing Celiac Disease

Objective To compare strategies for diagnosing celiac disease (CD). Methods A decision analytic model was used to compare five strategies on diagnostic performance and costs. Results First, tTG screening alone is the least costly strategy ($22/individual). While the NPV is high (99.8%), the PPV is low (63.4%). Second, if tTG-positive patients undergo esophagogastroduodenoscopy (EGD) to confirm CD, the PPV increases to 100% ($2,237/false-positive diagnosis avoided). Third, if EGDs are restricted to only those who are both tTG and HLA DQ2/8 positive, costs are slightly reduced ($59 vs. $63/individual), while PPV and NPV remain unchanged. Fourth, screening tTG-negative patients for IgA deficiency increases the NPV to 99.9% ($32,605/false-negative diagnosis avoided). Sensitivity analyses revealed that as the prevalence of CD increases, the cost of avoiding a false-positive diagnosis by adding EGD to the tTG alone strategy increases considerably. Conclusions When the pre-test probability of CD is low, patients with positive tTG serology should undergo EGD with biopsy—either directly or after positive screening for HLA DQ2/8—to confirm CD. As the pre-test probability of CD increases, the added cost of EGD should be weighed against the consequences of a false-positive diagnosis. Routinely screening for IgA deficiency in order to avoid a false-negative diagnosis is quite costly.     

Usefulness of Antibodies to Deamidated Gliadin Peptides in Celiac Disease Diagnosis and Follow-up

The prevalence of the recently described deamidated gliadin peptide antibodies was compared with that of the routinely used antigliadin, antiendomysial, and tissue transglutaminase antibodies in the sera of 128 untreated celiac patients and 134 controls. Sensitivity and specificity for celiac disease were 83.6 and 90.3% for IgA and 84.4 and 98.5% for IgG antibodies to deamidated gliadin peptides. The new test displayed higher diagnostic accuracy than antigliadin antibodies and, although less sensitive than antiendomysial and tissue transglutaminase antibodies, showed significantly higher specificity than tissue transglutaminase antibodies (P < 0.001). Persistence of peptide antibodies after gluten withdrawal was an expression of low compliance with the diet and of the lack of improvement of the intestinal mucosa. The combined use of tissue transglutaminase and deamidated gliadin peptide antibodies seems to be a very useful tool for celiac disease diagnosis. Moreover, antibodies to deamidated gliadin peptides can be helpful in disease follow-up.     

Capsule Endoscopy Findings in Celiac Disease

Capsule endoscopy (CE) is a noninvasive imaging method used to evaluate intestinal mucosa. We aimed to examine intestinal mucosal changes in celiac disease (CD) with CE. Eight untreated patients who had anti-endomysial antibody-positive duodenal biopsy results consistent with CD were included in the study. Villous atrophy, scalloping, fissuring, and mosaic pattern (consistent with CD) were detected in seven patients; one patient was excluded for early meal consumption. No patchy involvement was found in the intestine or distal region of the intestine (ileum) in any of the patients. The common feature of all patients was that villous atrophy, scalloping, fissuring, and mosaic patterns detected in the proximal intestine gradually decreased towards the distal intestine. CE provided no diagnostic contribution to CD when compared with duodenal biopsy. It can be used to show villous atrophy in selected cases and to evaluate the extension of intestinal involvement in CD.     

Intestinal Permeability and Antigliadin Antibody Test for Monitoring Adult Patients with Celiac Disease

Celiac disease causes chronic inflammation of the intestinal mucosa and reduces surface absorption; after the withdrawal of gluten from the diet, there are clinical and histologic improvements. The intestinal permeability test and serologic tests are useful for confirming the diagnosis and monitoring patients. The goal of this study is to compare the antigliadin antibody (AGA) test with the intestinal permeability test for celiac patients on a gluten-free diet. The sample consisted of 22 celiac patients who were antigliadin immunoglobulin A–positive before treatment. After 12 months on a gluten-free diet, AGA testing was repeated and the intestinal permeability test was performed. A control group was composed of 11 healthy individuals. AGA remained positive in 40.9% of celiac patients, and the mean urinary lactulose excretion was 10.27%, that of mannitol was 10.18%, and the lactulose/mannitol ratio was 1.02. In the subgroup in which antigliadin became negative (59.1%), the value for lactulose was 3.79%, that for mannitol was 11.12%, the lactulose/mannitol ratio was 0.38, and the p value was less than 0.0001, 0.66, and less than 0.0001, respectively. When the two celiac subgroups were compared with the control group, the urinary lactulose excretion and the lactulose/mannitol ratio was less in the control group, whereas urinary mannitol excretion was greater. The p values were less than 0.0001 for the three variables, suggesting persistent lesions in mucosa of both subgroups, although to a lesser degree for those that became AGA negative. It is concluded that intestinal permeability allows a more precise clinical physiopathologic correlation than antigliadin and offers more information for the monitoring of these patients.     

Delay in Diagnosis of Celiac Disease in Patients Without Gastrointestinal Complaints

Purpose

The purpose of our study is to investigate the delay in diagnosis of patients with biopsy-proven celiac disease in those who present with gastrointestinal complaints vs nongastrointestinal complaints at our tertiary care center. Celiac disease is an autoimmune disorder that affects approximately 1% of the population worldwide. Celiac disease can have variable clinical presentations; it can be characterized by predominately gastrointestinal symptoms, or it may present without any gastrointestinal symptoms.

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.     

Silent Celiac Disease Activated by Pancreaticoduodenectomy

Diarrhea and weight loss are common after pancreaticoduodenectomy, and arise from varying etiologies. An uncommon but important cause for these symptoms is the postoperative activation of silent celiac disease. We sought to describe the clinical presentation, diagnosis, treatment, and follow-up of a series of patients with silent celiac disease unmasked after pancreaticoduodenectomy, and to summarize the existing case reports on this association. A search of the electronic medical record at our institution was performed cross-referencing terms associated with celiac disease and pancreaticoduodenectomy for the years 1976–2004. Cases were then reviewed to ensure that no signs or symptoms attributable to celiac disease were present preoperatively. Seven patients were identified; five were male, and the median age was 56. All patients underwent surgery for a presumed pancreatic or ampullary malignancy. Six patients developed symptoms ultimately attributable to celiac disease immediately after pancreaticoduodenectomy, most commonly diarrhea and weight loss. A single patient had silent celiac disease incidentally diagnosed at pancreaticoduodenectomy that remained silent postoperatively on an unrestricted diet. Symptoms completely resolved in 4 of 6 patients after initiation of a gluten-free diet, with partial improvement in the remaining 2 patients. The median delay from pancreaticoduodenectomy to diagnosis of celiac disease in the 6 symptomatic patients was 6 months. Clinicians should consider celiac disease as a potential diagnosis in patients with failure to thrive and diarrhea after pancreaticoduodenectomy. This entity is uncommon, but may be underrecognized. The underlying mechanism may relate to an increased antigenic load secondary to postsurgical changes in intestinal physiology.     

Regulatory T-Cell Function Is Impaired in Celiac Disease

Celiac disease (CD) is characterized by intolerance to gluten and high risk of developing autoimmune phenomena. Possible defects in immune tolerance could have a role in the pathogenesis of the disease. As regulatory T-cells (Tregs) are the main population involved in maintaining peripheral tolerance, we investigated the number of these cells in celiac patients as compared with healthy donors. Moreover, we analyzed the suppressive function of CD4+CD25+ T-cells from celiac disease patients and controls on autologous responder T-cells (CD4+CD25−). The percentage of CD4+CD25+FOXP3+ cells was not different in celiacs and in healthy controls, and among positive cells the level of expression of the two regulatory markers was comparable. However, the suppressor activity of Tregs was significantly impaired in CD patients. These results suggest that a defect in Tregs function could play a role in the pathogenesis of CD and in CD-associated autoimmunity.     

Intestinal Diffuse Large B-Cell Lymphoma Associated with Celiac Disease: A Japanese Case

Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well known to be associated with celiac disease (CD), an enteropathic disorder with a propensity for certain racial and genetic backgrounds. CD is typically characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies in the sera, and microscopical findings of the intestinal mucosa, which resolve with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD and the associated NHL have been supposed to be quite rare, and studies concerning the frequency of CD or its relationship with NHL are scarce. We describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma associated with CD. Following multi-combined chemotherapy, the patient's lymphoma has been in a state of complete response, and his GI symptoms have improved with a GFD. This case suggests that the possibility of CD and its association with intestinal NHL should be kept in mind, even in Asian populations.     

Sarcoidosis in Patients with Celiac Disease

Purpose Several case reports and European studies have suggested an association between sarcoidosis and celiac disease; however, they have been inconsistent. We therefore analyzed a large cohort of celiac-disease patients to assess this association. Methods An anonymized database of patients with celiac disease was reviewed to determine the number of patients with sarcoidosis. Age- and gender-adjusted standardized morbidity ratios with corresponding 95% confidence intervals (CI) were calculated by comparing results to US-population-derived prevalence data. Results Ten patients were found to have a comorbid diagnosis of sarcoidosis, representing an age- and gender-adjusted standardized morbidity ratio of 36.8 (95% CI 26.7–50.9). Conclusions In this cohort of patients with celiac disease, there was a significantly increased risk of sarcoidosis when compared with the American white population. This further strengthens prior associations that have been made suggesting a shared mechanism behind the etiologies of celiac disease and sarcoidosis.     

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 nonHLA 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 antiendomysial 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.     

Pulmonary Hemosiderosis in Association with Celiac Disease

A 15-year-old male had a history of increasing dyspnea on exertion, cough, sputum production, fever, weakness, hemoptysis, and diarrhea. Chest radiography demonstrated bilateral alveolar consolidation. Bronchoalveolar lavage fluid analysis revealed extensive hemosiderin-laden alveolar macrophages. On the basis of iron deficiency anemia, diarrhea, raised antigliadin and antiendomysial antibodies, widespread villous atrophy, and crypt hyperplasia on intestinal biopsy, celiac disease was diagnosed. After treatment with a gluten-free diet, all his clinical symptoms and radiographic findings improved within two weeks.     

Anti-transglutaminase IgA ELISA: Clinical Potential and Drawbacks in Celiac Disease Diagnosis

Background: Since the identification of tissue transglutaminase (tTG) as the antigen for the antiendomysial antibodies (EMA), several antigen-specific immunoassays have been reported for celiac disease (CD) screening. A first objective was to evaluate the suitability for CD screening of three different IgA tTG ELISAs, two of them based on guinea pig liver tTG (gp-tTG) (an in-house ELISA with a partially purified extract and a commercial ELISA with purified gp-tTG antigen) and a third recombinant human tTG (rh-tTG) ELISA. The results are compared with EMA and with the final clinical diagnosis. A second objective was to analyze antibody reactivities in those patients with anti-tTG and EMA discrepancies. Methods: ELISA and EMA tests were used to measure IgA anti-tTG levels in sera from 259 patients (107 had CD and 72 had Type I diabetes mellitus). Results: The purified gp-tTG ELISA was highly sensitive (97.7%) and specific (98.8%) in the detection of CD, almost equaling EMA. Rh-tTG ELISA did not improved the sensitivity of EMA, but its specificity was slightly superior. Immunoblot analysis with partially purified gp-tTG extract, the antigen most frequently used for anti-tTG detection, showed that the majority of false positives were due to IgA reactivities to contaminant proteins present in the liver antigenic extract. This low specificity was particularly problematic in diabetics. Conclusion: Purified tTG ELISAs, either with purified guinea pig liver or recombinant human antigens, can be used as quantitative and observer-independent alternatives to the traditional and time-consuming EMA in the screening of CD.