Zulema Kogan

Value of endoscopic markers in celiac disease

Duodenoscopy in celiac disease has identified several markers of the disease. Our aim was to evaluate, in a prospective study, the usefulness of the different endoscopic features in 100 consecutive cases referred to endoscopy for intestinal biopsy. Histological examination of duodenal samples showed severe villous atrophy (grade III/IV) in 36 patients. Of these patients, 34 had endoscopic markers suggestive of celiac disease. These were reduction in number or loss of Kerkrings folds (in 27), mosaic pattern (14), scalloped folds (12), and visibility of the underlying blood vessels (5). Endoscopic visualization of these markers had a sensitivity of 94%, a specificity of 92%, and a positive predictive value of 84%. Reduction in number, or loss of, Kerkrings folds was the most sensitive (76%) and specific (98%) single endoscopic change indicating celiac disease. Duodenoscopy permitted diagnosis in three of four asymptomatic patients in a group of 24 first-degree relatives of celiac disease patients. We conclude that endoscopy of distal duodenum is a sensitive and specific indicator of celiac disease.

Successful treatment of retractile mesenteritis with oral progesterone

Retractile mesenteritis is a rare inflammatory mesenteric disorder that involves the intestine secondarily. The natural history of this process is diverse, but most patients require some empiric therapeutic measures. Up to now, pharmacological therapy has included corticosteroids, colchicine, and immunosuppressive drugs. Although these drugs are successful in most patients, some have been refractory to these therapies and, in others, the beneficial effects were counterbalanced by adverse reactions. Many patients require surgery, but most have poor results. This report describes a 42-year-old man with histologically proven retractile mesenteritis refractory to surgical intervention who had a good response to oral progesterone (10 mg/day for 6 months) with complete disappearance of tumor mass and clinical symptoms. No adverse effects were detected. Current knowledge about the mechanism by which progesterone affects fibrogenesis is scanty. It seems likely that progesterone down-regulates proliferation and metabolism of fibroblasts and fibrogenesis.

Azathioprine in refractory sprue: results from a prospective, open-label study

OBJECTIVE:Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue.METHODS:We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCRγ gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8–12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non-placebo-controlled study using azathioprine (2 mg/kg/day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n = 7) as well as enteral (n = 6) and parenteral nutrition (n = 5) were administered during the trial.RESULTS:After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up.CONCLUSIONS:The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.

Characterization of gastric mucosal lesions in patients with celiac disease: a prospective controlled study

Objective:Several studies have demonstrated that chronic exposure to gluten may damage the structure and function of the gastric mucosa in gluten-sensitive patients. However, until now, these abnormalities have been incompletely studied. Our purpose in the present study was to characterize, in a prospective controlled study, the endoscopic and histological appearance of the gastric mucosa in a large cohort of patients with celiac disease with and without Helicobacter pylori (H. pylori) infection.Methods:We evaluated biopsy specimens taken from the gastric body and antrum of 218 individuals who underwent upper endoscopy for small bowel biopsy. One hundred-four patients had celiac disease (80 of them at the time of diagnosis-untreated). In 114 subjects celiac disease was excluded.Results:Endoscopic findings did not show a difference between the groups. The prevalence of cases with normal gastric mucosa, chronic superficial gastritis, and atrophic gastritis was similar in patients and controls. Similarly, presence of metaplasia, inflammatory activity, and lymphoid follicles and aggregates did not show differences between the groups. Histological or serological evidence of H. pylori infection was detected in 86% of patients (82% of untreated celiacs and 95% of those on those taking treatment). The infection was highly prevalent in patients (89%) and controls (97%) diagnosed with chronic gastritis. Untreated patients had a significant greater IEL count in the antrum and corpus than controls (p < 0.0001 and p < 0.001, respectively). A global analysis of the data on intraepithelial lymphocyte (IEL) counts in the different populations suggest that the inflammatory state may represent the cumulative effect of H. pylori infection and gluten sensitivity. Only three patients had IEL infiltration compatible with diagnosis of lymphocytic gastritis (count >25%) and three other patients had borderline counts.Conclusions:According to our results, celiac disease patients presented a similar prevalence of gastric mucosal abnormalities compared with the control population. Evidence of H. pylori infection was very high compared with the prevalence in the general Argentine population. As a particular observation in our celiac population, the disease was rarely associated with lymphocytic gastritis. We suggest that the chronic inflammatory state evidenced by a gastric mucosal lymphocyte infiltration may be secondary to the combination of H. pylori infection and chronic gluten ingestion in gluten-sensitive subjects.

The natural history of gluten sensitivity : Report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives

OBJECTIVE:Early studies revealed that up to 50% of nonatrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment.METHODS:After a median time of 86 months (range: 42–102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy.RESULTS:At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype.CONCLUSIONS:Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.

Sugar tests detect celiac disease among first-degree relatives

OBJECTIVES:First-degree relatives of patients with celiac disease are at high risk for developing the disease themselves. Detection of serum antibodies and intestinal permeability tests have been useful to identify candidates for intestinal biopsies. Recently it was demonstrated that abnormal sucrose permeability is a very sensitive marker of active disease. Our objectives in this prospective study were (1) to assess the screening value of permeability tests, and (2) to compare the usefulness of these markers with that of the celiac disease-related serology in screening for celiac disease in a cohort of first-degree relatives of well-known patients.METHODS:We performed sugar tests in 66 first-degree relatives of probands. Subjects ingested 450 ml of a solution containing sucrose (100 g), lactulose (5 g), and mannitol (2 g). Subsequently, a complete overnight urine collection was obtained. Measurement of sugars was performed by high-performance liquid chromatography. All relatives were evaluated for antigliadin (type IgA and IgG) and endomysial antibodies and subjects positive for any test underwent intestinal biopsy.RESULTS:Twelve relatives were diagnosed as having small intestinal mucosal atrophy. Increased sucrose permeability was detected in 9 (75%) of these patients. Four false-positive determinations were found but all had gastric erosions, which is known to increase sucrose permeability independently of duodenal damage. Increased lactulose/mannitol ratios were observed in all new celiac patients. An additional nine relatives had positive results; however, four of them did not accept intestinal biopsy and the remaining five did not seem to have histological evidence of disease. Endomysial antibodies were detected in 11 of 12 patients and no false-positive cases were observed. Antigliadin antibodies were 75% sensitive and 88% specific.CONCLUSIONS:Our study demonstrated that screening using the endomysial antibody test is highly sensitive and specific for detecting celiac disease; however, almost 10% can be missed. The addition of lactulose/mannitol permeability testing to the screening protocol allowed us to detect all relatives who actually presented with evidence of gluten sensitivity. Sucrose permeability exhibited a lower sensitivity; however, it did detect other endoscopically visible lesions.

Gluten sensitivity in patients with primary biliary cirrhosis.

Objective:Whereas celiac disease and primary biliary cirrhosis have been reported to coexist in the same patient, the frequency of this relationship has not been clarified. Nowadays, the concept of celiac disease has been extended from that of a severe enteropathy to a broader concept of gluten-driven intestinal immunological response. In this study we assessed features of gluten sensitivity in a cohort of patients with primary biliary cirrhosis.Methods:Ten patients with primary biliary cirrhosis were evaluated a mean of 2 yr after diagnosis. The following features of gluten sensitivity were assessed: serum antigliadin and endomysial antibodies, small bowel histology (degree of atrophy and quantitative histological parameters), the presence of the typical celiac HLA genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa after local gluten instillation (rectal gluten challenge).Results:Overall, three patients presented evidence of gluten sensitivity. AH three had abnormal liters of antigliadin antibody type IgA and one was positive for endomysial antibody. Two patients had partial villous atrophy. The rectal gluten challenge showed a celiac-like response, evidenced by an increase in intraepithelial lymphocyte infiltration after gluten exposure, in the three patients. The characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in three patients. One of them also exhibited other features of gluten sensitivity. However, despite evidence of gluten intolerance, patients had minimal or no symptoms characteristic of celiac disease.Conclusion:We detected features of gluten sensitivity in a high proportion of patients with primary biliary cirrhosis. Further studies should be performed to elucidate the clinical significance of this association.

Increased mucosal levels of leukotriene B4 in pouchitis : evidence for a persistent inflammatory state

Design and Methods In order to evaluate its possible role in the pathogenesis of pouchitis we measured the release, into the incubation medium, of leukotriene B4 from mucosal samples from patients with ileal pouch-anal anastomosis and correlated release with clinical, endoscopic and histological features. Results Leukotriene B4 release was significantly elevated in patients with active pouchitis in comparison to those with a normal pouch mucosa (P<0.007). No overlap was observed between leukotriene B4 levels from patients with active pouchitis samples and those obtained from individuals without-pouchitis. Effective treatment of pouchitis was associated with a significant reduction in leukotriene B4 mucosal release to the incubation medium (P<0.03). However, even in remission, levels of leukotriene B4 release remained significantly increased in these patients in comparison to people who never experienced pouchitis (P< 0.003). A modest correlation was observed between pouchitis disease activity index and leukotriene B4 release (r = 0.596; P< 0.01). Conclusion These results suggest that the increased production of leukotriene B4 may be implicated in the pathogenesis of pouchitis. The persistence of an increased mucosal release of leukotriene B4 in pouchitis patients during clinical remission suggests the presence of a chronic, ongoing, underlying inflammatory process.