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Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA—two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.

The presence of circulating autoantibodies to gut enterocytes has been very rarely described in adults and is considered a possible cause of refractory sprue. Our aims was to describe the case of an adult patient with serum anti-enterocyte autoantibodies associated with a clinical picture characterized by involvement of both the small intestine and colon. A female, age 50, had suffered from diarrhea with mucus and blood, abdominal pain, thinness, anemia, and leukopenia since the age of 20. She also suffered from HCV infection and had mild chronic hepatitis. Family history was positive for autoimmunity. Symptoms were reported to worsen after eating gluten-containing foods, but anti-transglutaminase and anti-endomysial antibodies were negative. Intestinal histology showed mild, patch villous atrophy with a high intraepithelial lymphocyte count, but a normal number of intraepithelial lymphocytes carrying the gamma/delta+ receptor. HLA was: A11, A31 (19), B52 (5), DR 15 (2), DR 14 (6), DR 51, DR 52, DQ1. Colonoscopy did not show ulcerations or erosions and colon histology showed a moderate inflammatory infiltrate without minor crypt distortion or granuloma. RAST tests were positive for lactalbumin, lactoglobulin, casein, egg, and gliadin. After commencement of an oligoantigenic diet, stool frequency initially decreased, but the presence of mucus in the stools persisted, with episodes of bloody diarrhea. After one year of diet, nutritional parameters were low and anemia associated with a low leukocyte count persisted. Upper and lower gastrointestinal endoscopy and histology of the small intestine and colon were virtually unchanged. Consequently, natural autoantibodies and enterocyte autoantibodies were assayed. The patient was positive for IgG class enterocyte autoantibodies at a titer of 1:34. No other organ-specific or non-organ-specific autoantibodies were positive. Prednisolone treatment was started and the symptoms improved. After one year of this treatment plus elimination diet she was reevaluated. Bowel movement frequency was normal, body weight increased, and the asthenia had completely regressed. IgG anti-enterocyte autoantibodies were absent. Histology of the distal duodenum showed a normal villus/crypt ratio and IEL infiltration was reduced. Colon histology showed a reduction in inflammatory infiltrate in the lamina propria. In conclusion, we report a case of generalized gut disorder in an adult patient, affecting both the small intestine and the colon and characterized by the presence of circulating anti-enterocyte autoantibodies. Systematic testing for enterocyte autoantibodies should be performed not only in patients with refractory sprue, but also in subjects with upper and lower intestinal symptoms who have not been definitively diagnosed.

Several reports have indicated that fecal elastase-1 (EL-1) determination is a new, sensitive, and specific noninvasive pancreatic function test; however, very few patients with malabsorption due to small intestine diseases have been included in the previous studies. The aim of the study was to compare the diagnostic accuracy of fecal EL-1 and fecal chymotrypsin (FCT) in distinguishing between pancreatic maldigestion and intestinal malabsorption. Three groups of subjects were studied: group A included 49 patients with known cystic fibrosis (25 males, median age 5 years); group B included 43 subjects with various small intestine diseases (17 males, median age 6 years); and group C included 45 children without any history of gastrointestinal disease (22 males, median age 5 years). In all patients, stools were collected for 72 h on a standard diet and fecal EL-1, FCT, and steatocrit tests were performed. Both EL-1 and FCT were below normal limits in all CF patients with pancreatic maldigestion not treated with pancreatic enzyme (100% sensitivity for both assays); El-1, but not FCT, was also below normal in all the CF patients with pancreatic maldigestion treated with pancreatic extracts. Both EL-1 and FCT values in the CF group were significantly lower than in subjects with various small intestinal diseases and in children without any history of gastrointestinal disease (P < 0.0001). FCT, but not EL-1, values showed an inverse statistically significant correlation with steatocrit values in the whole CF group (P < 0.001); FCT was below normal in three of four CF patients with steatorrhea on pancreatic enzyme therapy. Both EL-1 and FCT had 100% specificity when calculated in children without any history of gastrointestinal disease; in contrast, specificity was 86% for EL-1 and 76% for FCT if we considered the control group with small intestinal diseases: low EL-1 was observed in two cases of intestinal giardiasis, two cases of short bowel syndrome, one case of celiac disease, and one case of intestinal pseudobstruction; FCT was abnormal in four cases of intestinal giardiasis, three cases of celiac disease, one case of short bowel syndrome, one case of Crohn's disease, and one case of intestinal pseudobstruction. Diagnostic accuracy was 92% for fecal EL-1 and 82% for FCT. Steatocrit values were over the normal limit in 11 patients with small intestine diseases; in 7/11 of these patients at least one of the pancreatic test results was below the normal limit. In conclusions, in patients with CF, fecal EL-1 determination is not more sensitive than FCT in identifying pancreatic maldigestion; however, fecal EL-1 assay is more specific than FCT determination in distinguishing pancreatic maldigestion from intestinal malabsorption.

Recent studies have pointed to the relationshipbetween iron deficiency anemia and celiac disease,although data on the prevalence of celiac disease inanemic patients have been conflicting, and there is no agreement on the best screening procedurefor CD in these patients. Our aims were to evaluate therelationship between anemia and celiac disease (CD) fromtwo different points of view — the hematology clinic and the pediatric gastroenterologydepartment — and to evaluate the utility ofanti-endomysial antibody determination in screeninganemic patients for CD using human umbilical cord assubstrate. We studied 130 patients with CD (58 males, 72females; median age 18 months) diagnosed at a departmentof Pediatric Gastroenterology, and 85 patients with irondeficiency anemia (38 males, 47 females; median age 48 years) observed at a hematologyoutpatient clinic. From the 85 adult patients with irondeficiency anemia, we selected a subgroup of 25 subjectswith no improvement in Hb after two months of iron therapy (80 mg/day orally). Routinehematochemical tests were performed in all 215 patients.All pediatric and adult subjects underwent immunologicalscreening for celiac disease (AGA and EmA assay);intestinal biopsy was also performed on patients testingpositive. In the adult anemic patients a serum samplewas stored at –20°C on first observation, andafter 6-18 months EmA on human umbilical cord wereassayed. In the pediatric patients with CD, anemia wasobserved in 91/130 patients (70% of cases, the mostfrequent symptom after poor growth); however, this wasthe only presenting symptom of CD in 2/130 patients (1.5% of cases). Anemia was sideropenic in41/91 patients (iron

In this study we aimed to correlate liverhistology and the presence of hepatitis C virus (HCV)viremia, genotype, and quantity of HCV genome in 19positive and 11 RIBA II indeterminate patientspresenting persistently normal ALT values over 24 monthsbefore biopsy. In addition, after biopsy serum ALTvalues were monitored monthly for a mean follow-upperiod of 24.8 months, after which patients werereevaluated for RIBA II and the presence of viremia.Sixteen patients (53%) were serum HCV-RNA-positive; 13of them (68%) were confirmed positive and 3 (27%)indeterminate on RIBA II. Histology of the HCV-RNA-positive patients showed eight cases of CPH (one case ofgenotype 1a; four cases type 1b; three cases type 2),six cases of CAH (three cases type 1b, three cases type2), one case of CLH (type not determined), and one case of normal liver (NL) (type 1b).Histology of the HCV-RNA-negative patients showed fourcases of CPH, one case of CAH, two cases of CLH, andseven cases of NL. During the follow-up period ninepatients (30%) presented slight increases in ALT values(

To determine the relationship between pancreatic secretory capacity and nutritional status in celiac patients, we studied 52 patients with celiac disease (24 males, 28 females; age range 6-36 months) and 30 healthy control subjects (14 males, 16 females; age range 6-42 months). A secretin-cerulein test was performed on all patients, and levels of serum albumin and plasma fibronectin were assayed. In addition, weight/height ratios were calculated in the celiacs, who were then divided into three groups on this basis, as follows: celiacs with weight/height ratioor = 3rd percentile; those with weight/height ratio between the 4th and 10th percentiles; and those with weight/height ratio10th percentile. There was no significant difference in the duodenal output of chymotrypsin, phospholipase and lipase between these groups. When the total celiac group was compared to control subjects, only lipase levels were significantly lower (P0.009). However, subnormal values in one or more pancreatic enzymes were observed in 15/52 celiacs (29%). A residual enzyme activity10% of normal secretory capacity, was also found in 4/52 patients. There was no correlation between the output of the various pancreatic enzymes and levels of albumin, fibronectin, and weight/height ratios in the patients. Furthermore, there was no difference in weight/height ratios and levels of albumin and fibronectin between the celiac subjects with pancreatic deficiency and those with normal pancreatic function. We conclude that a mild/moderate pancreatic insufficiency is quite frequent in celiacs, but that it may be completely independent of nutritional status; further studies are therefore required to shed light on its pathogenesis.

The validity of pancreatic enzyme substitution therapy in the two months following diagnosis of celiac disease was investigated. Twenty patients (8 males, 12 females), mean age 14.2 months (group A) received an enzyme substitution preparation. The control group (group B) included 20 patients (9 males, 11 females), mean age 14.5 months, treated with placebo. Before starting treatment, we performed a stratification for age, weight-for-age at diagnosis, and degree of pancreatic insufficiency. The therapies were then administered randomly in double-blind fashion. On diagnosis and 30 and 60 days after commencement of a gluten-free diet with identical calorie intake in both groups, a series of anthropometric variables were determined. After 30 days weight increase in group A patients was significantly higher (in grams) than in group B: 1131 +/- 461 vs 732 +/- 399 (P < 0.006). Weight-for-age increase also was greater in group A than in group B: 9.2 +/- 5.1% vs 5.0 +/- 4.0% (P < 0.002). The increase in height Z score, weight-for-height, arm circumference, and subscapular and tricipital fold measurements were greater in group A patients than those in group B, but the difference was not significant. After 60 days of therapy none of the parameters considered were significantly different in the two groups. We concluded that pancreatic enzyme therapy is certainly useful in the first 30 days after diagnosis of celiac disease.

In patients with pancreatic exocrine insufficiency, the use of pancreatic enzyme does not abolish steatorrhea in some cases. We carried out a long-term prospective study in an attempt to clarify the effectiveness of the associated use of famotidine to enzymatic supplementation on fat absorption and nutritional parameters of patients with pancreatic insufficiency due to cystic fibrosis. We studied 10 patients, mean age 12.5 years, with persistent steatorrhea on enzymatic supplementation. A double-blind crossover design was used and famotidine (1 mg/kg/day) or placebo was given as adjuvant to enzymatic preparations for either of two six-month periods. A statistically significative reduction in fecal wet weight (P less than 0.0001), an improvement in the coefficient of fat absorption (P less than 0.01) and in the steatocrit values (P less than 0.028) were found on famotidine. Moreover, the weight and the height increases were greater after famotidine than after placebo period (respectively, P less than 0.012 and P less than 0.01); also the serum calcium and triglycerides levels were higher after the period on famotidine (respectively, P less than 0.0025 and P less than 0.025). No adverse effects of famotidine were noted. These data suggest that famotidine is a useful adjuvant to pancreatic enzyme therapy in patients with severe pancreatic insufficiency and persistent maldigestion on large doses of pancreatic supplements; in fact, famotidine improves not only fat absorption but the nutritional status of the patients.