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[Intestinal B-mode sonography in patients with endemic sprue. Intestinal sonography in endemic sprue].

AIM: The value of ultrasonography in the diagnosis, follow-up and for the detection of complications in patients with celiac sprue has not yet been sufficiently evaluated. A pronounced back and forth motility with echo-rich hump reflexes in a fluid-filled small bowel with a reduction of Kerckring's plicae circulares and with a loss of their density and uniformity was empirically defined as a diagnostic sign of celiac sprue. In the present study, the sonographic signs of celiac sprue were examined as an indicator of active sprue. METHOD: 50 patients with histologically proven celiac sprue were examined with real time ultrasonography (3.5-7 MHz). The detection or exclusion of the defined sonographic signs of celiac sprue with intensified motility and reduction of Kerckring's plicae circulares with a loss of their density and uniformity were evaluated by two independent examiners and documented without knowledge of the clinical findings. The clinical activity (active vs. remission) was assessed according to clinical criteria (diarrhea, steatorrhea, weight loss). 38 healthy subjects and 50 patients with Crohn's disease served as controls. RESULTS: In all 138 patients and controls adequate visualization of the bowel was achieved. In 16/50 (32%) patients with active celiac sprue changes of motility and reduction of Kerckring's plicae circulares with a loss of their density and uniformity were detected, whereas all 34/50 (68%) of patients with celiac sprue in remission did not have this pattern. In none of the controls with Crohn's disease or in the healthy subjects comparative sonographic signs of active celiac sprue were observed. In four patients with active celiac sprue a circumscript echopoor tumor of the small bowel wall could be sonographically detected, which turned out to be T-cell lymphoma in three and a carcinoma of the small intestine in one patient. An increased number of and/or enlarged mesenteric lymph nodes were found in patients with active celiac sprue. CONCLUSION: Changes of motility and reduction of Kerckring's plicae circulares with loss of density and uniformity at ultrasonography are a reliable indicator of active celiac sprue.

Adult↗

Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis?

Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.

Adolescent↗

Push enteroscopy in celiac sprue and refractory sprue.

BACKGROUND: The aim of this study was to determine in patients with sprue whether jejunal endoscopy improves the diagnostic yield or provides information that may modify management, when compared with evaluation limited to the duodenum. METHODS: From January 1994 to June 1998, a total of 31 patients (6 men, 25 women, mean age 41 years) were prospectively evaluated by push enteroscopy. They were divided into two groups: (1) celiac disease at different stages of activity (n = 23) and (2) refractory sprue (n = 8). The endoscopic and histologic findings in the duodenum and in the jejunum were compared. RESULTS: Celiac disease: In 19 patients, endoscopic and histologic findings in the duodenum and jejunum were similar; in four patients villous atrophy was more severe in the duodenum than in the jejunum. Refractory sprue: In 5 of 8 patients, enteroscopy revealed ulcerative jejunitis, whereas ulcerations were found in the duodenum in only one case. CONCLUSION: In refractory sprue, push enteroscopy with jejunal biopsies was of diagnostic value in 50% of cases demonstrating ulcerative jejunitis, whereas it did not modify the management of patients with responsive celiac disease.

Adult↗

Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue.

BACKGROUND: Clonal T cell receptor (TCR) gene rearrangements and loss of T cell antigens such as CD8 and TCR-beta in intraepithelial lymphocytes (IELs) may indicate the development of an enteropathy-type intestinal T cell lymphoma (EITCL) in patients with refractory sprue. AIMS: To define the diagnostic value of these markers in duodenal biopsies from patients with villous atrophy as a result of various underlying disorders. PATIENTS AND METHODS: Duodenal biopsies from eight patients with coeliac disease and five patients with villous atrophy caused by defined disorders were compared with three patients with refractory sprue evolving into overt EITCL, two patients with ulcerative jejunitis, and with eight patients with overt EITCL, for expression of CD3, CD4, CD8, and TCR-beta in IELs using immunohistochemistry and for clonal TCR-gamma gene rearrangements using polymerase chain reaction. In addition, biopsies from six consecutive patients with refractory sprue of uncertain cause were examined. RESULTS: Clonal TCR-gamma gene rearrangements were found in all resected tumours of patients with EITCL, in 3/8 duodenal biopsies of patients with EITCL, in 2/2 patients with ulcerative jejunitis, in 2/3 patients with refractory sprue evolving into overt EITCL, and in 1/6 patients with refractory sprue. No rearrangements were found in biopsies from patients with refractory sprue caused by defined disorders or those with coeliac disease. Clonality in duodenal biopsies was associated with an abnormal phenotype of IELs in all cases and in all but one case in patients with evidence of underlying coeliac disease. Specificity for detection of an EITCL using immunohistology was 77% for CD8 and for TCR-beta staining, and 100% for detection of a clonal TCR-gamma gene rearrangement. Sensitivity was 62% for staining with CD8 and clonality investigation, while sensitivity reached 100% for TCR-beta staining in all investigated patients with EITCL. CONCLUSIONS: Clonal proliferations of phenotypically abnormal IELs in refractory sprue represent an early manifestation of EITCL, for which the term "sprue-like intestinal T cell lymphoma" is proposed. This constellation is also found in duodenal biopsies from patients with an overt EITCL and is not related to other sprue syndromes, resulting in a high specificity for detection of an EITCL or refractory sprue evolving into EITCL. Overt EITCL may develop directly from coeliac disease without a precursor lesion (refractory sprue with clonal IELs) being demonstrable in duodenal biopsies or via a "sprue-like intestinal T cell lymphoma". This latter entity is a complication of coeliac disease.

Adolescent↗

Tropical Sprue.

Tropical sprue is a disease that causes progressive villus atrophy in the small intestine, similar to nontropical (celiac) sprue. The loss of intestinal villi profoundly affects intestinal absorptive function, and patients with tropical or nontropical sprue present with malabsorption. Whereas the etiology of celiac sprue has been elucidated in considerable detail, the etiology of tropical sprue remains obscure. The favored hypothesis is that the disease is either initiated or sustained by a still-undefined infection. Patients with tropical sprue typically present with macrocytic anemia due to malabsorption of folate and/or vitamin B(12). Treatment of tropical sprue with folic acid replacement was introduced more than 50 years ago and has become standard medical treatment. Vitamin B(12) replacement is usually added if there is evidence of B(12) deficiency or malabsorption. Treatment of tropical sprue with folate and B(12) cures the macrocytic anemia and the accompanying glossitis, and often results in increased appetite and weight gain. However, even prolonged treatment with these vitamins fails to restore villus atrophy, and malabsorption usually persists. The benefit of antibiotic treatment of tropical sprue was first documented during World War II, when sulfonamides were used to treat epidemics of tropical sprue in British and Italian troops in India. Antibiotic treatment has since become the standard treatment, and tetracycline has replaced sulfonamides. The recommended length of treatment with tetracycline is 6 months and it is given in combination with folate. The treatment has been shown to normalize mucosal structure in the small intestine and resolve malabsorption in most patients with tropical sprue. However, there is a substantial relapse rate in treated patients who return to, or remain in, endemic areas in the tropics.

Journal Article↗

The sprue syndromes.

The sprue syndromes, tropical and nontropical sprue, were both described as disease entities in the 1880s and share similar morphological features with varying degrees of villus atrophy of the small intestinal mucosa, and both present clinically with malabsorption. Recent cell kinetic studies of the turnover of the intestinal epithelium in sprue have convincingly demonstrated that the flat mucosa is caused by increased efflux (cell death) with compensatory crypt hyperplasia. The pathogenetic insult in tropical sprue appears to be a persistent overgrowth of the small intestine by enteric pathogens after a bout of turista. The pathogenesis of nontropical sprue is determined by both genetic factors, demonstrated with a strong association with certain HLA haplotypes (B8, DR3, DR7 and DC3) and presumably also environmental events (virus infection?), which render the mucosa susceptible to gluten. The cause of the malabsorption syndrome is multifactorial and results from both intraluminal and cellular events. The digestion of proteins, carbohydrates, and lipids is compromised due to decreased pancreatic and biliary secretion. The absorption of the digestive products is also severely affected due to decreased activity of microvillus enzymes (dipeptidases and disaccharidases) and a presumed reduction in the number of transport carriers. The clinical presentation is identical and the distinction between tropical and nontropical sprue is based on the history (ie, exposure to a tropical environment) and the response to treatment. Tropical sprue is cured by treatment with tetracycline and folic acid, whereas nontropical sprue responds to a gluten-free diet. Nontropical sprue is associated with dermatitis herpetiformis by common genetic and morphological features, and the skin lesions in dermatitis herpetiformis are also responsive to a gluten-free diet. Finally, there appears to be an increased incidence of intestinal malignancies (lymphoma, adenocarcinoma) in nontropical sprue.

Celiac Disease↗

Epithelial barrier and ion transport in coeliac sprue: electrical measurements on intestinal aspiration biopsy specimens.

Epithelial barrier function and ion transport was studied in coeliac sprue using a miniaturised Ussing device for measurements on diagnostic aspiration biopsy specimens from the jejunum of untreated or gluten free nourished sprue patients, or from healthy controls. Pure epithelial resistance (Re) indicating epithelial barrier function was determined by transmural alternating current impedance analysis. It was reduced by 56% in acute sprue mean (SEM) (9 (1) omega.cm2) compared with controls (20(2) omega.cm2). In gluten free nourished sprue patients Re was only partly recovered (15 (1) omega.cm2). Subepithelial resistance (Rsub) was also changed from 28 (1) omega.cm2- in control to 17 (1) omega.cm2 in acute sprue because of the change in mucosal architecture, but was unchanged in gluten free nourished sprue patients (29 (4) omega.cm2). In acute sprue, unidirectional Na+ and Cl- fluxes were increased in both directions as a consequence of the decreased resistance. However, short circuit current (ISC) as well as Na+ and Cl- net fluxes were not significantly different from control. Subsequently, the electrogenic Cl- secretory system was investigated. After maximal stimulation with theophylline and prostaglandin E1, a Cl(-)-dependent increase in ISC was obtained in the sprue mucosa and control jejunum. It showed saturation characteristics and was blockable by serosal bumetanide. When compared with control, neither Km nor Vmax of this electrogenic Cl- secretion was significantly changed in coeliac sprue. In conclusion, a miniaturised Ussing device was used for transport measurements on intestinal biopsy specimens. In acute coeliac disease, the epithelial barrier of the jejunum was seriously disturbed. The active electrogenic Cl- secretory transport system was present in the sprue mucosa, but was not activated in the Ussing chamber in vitro when compared with control jejunum.

Acute Disease↗