Moderate Villous Atrophy Research Articles

2604 Celiac Disease: No Longer a Diagnosis of Exclusivity

INTRODUCTION: Celiac disease (CD) is a chronic autoimmune enteropathy that occurs in genetically susceptible individuals when exposed to gluten proteins. In the past, CD was thought to be exclusive to Caucasians of European descent. With the advent of serological screening tests, CD has become increasingly recognized in other ethnic populations around the world. CASE DESCRIPTION/METHODS: A 56-year-old female of Indian descent was evaluated for chronic epigastric abdominal pain. The pain did not radiate and worsened with certain movements and spicy foods. She also reported an occasional acidic taste suggestive of reflux. Medical history included arthritis, hyperlipidemia, and a cholecystectomy. A colonoscopy performed two years ago was unremarkable. She underwent an EGD which demonstrated a normal esophagus, mild antral gastritis, and flattening of duodenal villi. Biopsies were obtained and an anti-tissue transglutaminase (anti-tTG) IgA level was ordered for suspicion of CD. Histology of the duodenal mucosa revealed moderate villous atrophy and increased intraepithelial lymphocytes. Anti-tTG IgA levels were elevated at 39 U/mL (normal 0–3 U/mL). H. pylori testing was negative. CD was diagnosed based on the histological findings and positive serology. The patient was instructed to begin a gluten-free diet (GFD) and referred to a medical nutritionist for further assistance. After starting a GFD, she reported significant symptomatic improvement. DISCUSSION: Few population studies in the past have looked at the prevalence of CD in non-Caucasian ethnic groups where the disease may have been underdiagnosed. Several recent studies suggest that gluten intolerance is more common than previously estimated in certain populations. Cataldo et al reported that 26–49% of Indian children presenting to tertiary care hospitals with chronic diarrhea had been diagnosed with CD.1 And a review by Yachha et al of an earlier study from the UK found 20 of 106 CD patients to be of South Asian origin.2 This case highlights the changing global paradigm of CD prevalence and provides valuable insight for clinicians in Western countries serving diverse immigrant populations. In conclusion, we recommend that physicians assess for CD without racial bias if clinical suspicion warrants an evaluation.

AutochthonousLeishmania siamensisin Horse, Florida, USA

Autochthonous<i>Leishmania siamensis</i>in Horse, Florida, USA

Prevalence of celiac disease in multiple sclerosis

BackgroundCeliac disease (CD) is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS) patients and their first-degree relatives.MethodsWe analyzed the prevalence of serological, histological and genetic CD markers in a series of 72 MS patients and in their 126 first-degree relatives, compared to 123 healthy controls.ResultsTissue IgA-anti-transglutaminase-2 antibodies were positive in 7 MS patients (10%), compared to 3 healthy controls (2.4%) (p < 0.05). OR: 5.33 (CI-95%: 1.074-26.425). No differences were found in HLA-DQ2 markers between MS patients (29%) and controls (26%) (NS).We detected mild or moderate villous atrophy (Marsh III type) in duodenal biopsies, in 8 MS patients (11.1%). We also found a high proportion of CD among first-degree relatives: 23/126 (32%). Several associated diseases were detected, mainly dermatitis 41 (57%) and iron deficiency anemia in 28 (39%) MS patients. We also found in them, an increased frequency of circulating auto-antibodies such as anti-TPO in 19 (26%), ANA in 11 (15%) and AMA in 2 (3%).ConclusionsWe have found an increased prevalence of CD in 8 of the 72 MS patients (11.1%) and also in their first-degree relatives (23/126 [32%]). Therefore, increased efforts aimed at the early detection and dietary treatment of CD, among antibody-positive MS patients, are advisable.

Cross-Protection against a Human Enteric Coronavirus and a Virulent Bovine Enteric Coronavirus in Gnotobiotic Calves

A group 2 human coronavirus designated HECV-4408 was isolated from a child with acute diarrhea and is antigenically and genetically more closely related to bovine coronavirus (BCoV) than to human coronavirus OC43 (X. M. Zhang, W. Herbst, K. G. Kousoulas, and J. Storz, J. Med. Virol. 44:152-161, 1994). To determine whether HECV-4408 infects gnotobiotic calves and induces cross-protective immunity against the virulent enteric BCoV DB2 strain, gnotobiotic calves (n = 4) were orally inoculated with HECV-4408 and then challenged with BCoV DB2 at postinoculation day (PID) 21. All calves inoculated with HECV-4408 developed diarrhea at PID 3 to 4 lasting 5 to 9 days. Fecal and nasal virus shedding were first detected by reverse transcription-PCR at PID 3 to 4 and at PID 2 to 4, respectively. After challenge with bovine coronavirus, no diarrhea or virus shedding was detected in calves inoculated with HECV-4408, but a mock-inoculated calf developed diarrhea and fecal and nasal shedding. Fecal immunoglobulin A (IgA) and serum IgG antibodies were first detected at PID 7 and PID 14, respectively. At postchallenge day 7, serum IgG and fecal IgA antibody titers remained the same or increased only twofold compared to prechallenge titers. An additional two gnotobiotic calves were inoculated with HECV-4408 and euthanized at PID 5. Moderate villous atrophy was observed in the small intestines, and viral antigen was detected in villous enterocytes of the small and large intestines by immunohistochemistry. These results support and extend the previous report that HECV-4408 is likely a variant of bovine coronavirus. They confirm its infectivity for calves and complete cross-protection against a bovine coronavirus (DB2 strain) showing 98.2% amino acid identity to HECV-4408 in the S protein.

Duodenal Disaccharidase Activities in the Follow-up of Villous Atrophy in Coeliac Disease

Background: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. Methods: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade 1 = slight villous atrophy, that is, cryptic component 30%- 50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component &gt;90%. The enzyme activities of the disaccharidases were determined as U/g protein. Results: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity &lt;150 U/g protein), 86% for sucrase (&lt;40 U/g protein) and 71% for lactase (&lt;20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. Conclusions: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.

Duodenal Disaccharidase Activities in the Follow-up of Villous Atrophy in Coeliac Disease

Background: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. Methods: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade 1 = slight villous atrophy, that is, cryptic component 30%- 50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme activities of the disaccharidases were determined as U/g protein. Results: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. Conclusions: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.

Bovine viral diarrhea virus isolated from fetal calf serum enhances pathogenicity of attenuated transmissible gastroenteritis virus in neonatal pigs.

A bovine viral diarrhea virus (BVDV-C) was isolated from swine tissue culture cells used to attenuate the transmissible gastroenteritis virus (TGEV) after 68 passes. Piglets given a pure culture of BVDV-C developed clinical signs similar to those of a mild TGEV infection and recovered by 10 days postexposure. Villous blunting and fusion was observed in the small intestine, and a lymphocyte depletion was observed in Peyer's patches in the ileum. Piglets given a combination of BVDV-C and attenuated TGEV developed clinical signs similar to those of a virulent TGEV infection and were euthanized. The combined infection induced a generalized lymphocyte depletion throughout the lymphatic system and villous atrophy in the intestinal tract. Piglets exposed to a another type I strain of BVDV (NY-1) either alone or in combination with the attenuated TGEV had mild clinical signs similar to those of a TGEV infection. Moderate villous atrophy in the ileum and a lymphocyte depletion in the mesenteric lymph node were observed in these piglets postmortem. The data indicate a potential problem for diagnostic laboratories in relation to a diagnosis of virulent TGEV infections and in the field for young piglets exposed to a BVDV-contaminated TGEV vaccine.

Biology and pathogenicity of Eimeria neodebliecki Vetterling, 1965 in experimentally infected pigs

The endogenous development and pathogenicity of Eimeria neodebliecki Vetterling, 1965 are described in weaned pigs inoculated with 250 000 oocysts. The endogenous stages developed within the apical cytoplasm of the enterocytes of the middle and posterior jejunum. The asexual development comprised two generations of meronts. Immature and mature meronts were found in groups up to five per host cell. The first fully developed macrogametes and mature microgamonts were seen at 9 days post-infection (DPI). The prepatent period was 10 days, and the patent period lasted 6–8 days. Sporulation of oocysts was completed within 12 days at 25°C, and 16 days at 20°C. E. neodebliecki infection produced clinical signs of coccidiosis in weaned pigs which developed frothy or mucoid diarrhea from 9 to 12 DPI. Pathological changes were situated in the second half of the small intestine, with the predilection for the posterior jejunum. At 9 and 10 DPI, macroscopically, ranged from catarrhal to focal, pseudomembranous inflammatory lesions. Histopathological and SEM examinations revealed moderate villous atrophy with focal epithelial erosions and fibrinonecrotic material at the villous tips. E. neodebliecki is pathogenic for pigs and can be associated with clinical manifestation of diarrhea, stunted growth and poor condition in pigs.

EVALUATION OF CLINICAL AND LABORATORIAL PARAMETERS DURING LACTOSE ABSORPTION TEST: ORAL LOAD WWITH LACTOSE AQUEOUS SOLUTION AND COW'S MILK

Lactose absorption tests were studied in 7 malnourished infants with chronic diarrhea, 3 - 7 month old, with the aim to assess the value of some clinical and laboratory parameters evaluated during the oral load of lactose (2g/kg), both in aqueous solution (OLS) and after 7 days, with cow's milk (OLM). Mean “score z” weight/age, height/age and weight/height were, respectively:−3.0±1.6, −2.4±1.1 and −1.9±2.0. Mean d-xylose was 16.4±6.6 mg/dl and moderate villous atrophy was shown in jejunal biopsies. After overnight fasting, during lactose test, blood glucose, stool pH and reducing substances (RS) and hydrogen breath test were analyzed. After 180 min. we observed the following clinical features: abdominal distention in 6 patients loaded with OLS and OLM; increased bowel sounds were observed in 7/OLS and in 5/OLM; diarrhea in 5/OLS and in 4/OLM. Four/OLS and 3/OLM were nonabsorbers; pH less than 6 was observed in 4/OLS and in 3/OLM; mean RSwas 1.25±0.8 mg/dl with OLS and 0.25±0.0 mg/dl with OLM (p=0.015); H2 was 37.6±40.1 ppm with OLS and 8.9±5.3 ppm with OLM (p=0.07). In conclusion, our data showed similar clinical and laboratory findings with OLS and OLM. In addition, a better tolerance was found with cow's milk. The more sensitive tests were the stool reducing substances and the hydrogen breath test with oral lactose aqueous solution.

Intestinal Microsporidiosis in a Chilean Patient with Acquired Immunodeficiency Syndrome (AIDS)

A 24-year-old male patient with AIDS diagnosed in 1989, and with several episodes of pneumocystosis, was admitted because of a chronic diarrheic syndrome and severe epigastric pain. Endoscopy showed a granular duodenal mucosa. Light microscopy showed a moderate villous atrophy with round-cell inflammatory infiltration of the chorion. Giemsa, Ziehl-Neelsen, and Gram stains showed microsporidial spores measuring between 1.5 and 2 microns in the supranuclear cytoplasm of some enterocytes. Electron microscopy showed sporoblasts and spores consistent with Enterocytozoon bieneusi, with an apparently non-tubular, rather electron-dense polar filament showing up to 7 coils and also a microtubular internal structure with annular disposition, a finding which has not been adequately emphasized in the pertinent literature, probably representing a contractile property of the polar filament, rather than a mere duct for the parasitic sporoplasm to be inoculated.

Experimental Eimeria debliecki infections in nursing and weaned pigs

Three litters of six, 3-day-old nursing pigs were inoculated via a stomach tube with 8.0 × 10 5, 1.6 × 10 6 or 5.0 × 10 6 sporulated oocysts of Eimeria debliecki and four groups of six, 4-week-old weaned pigs were inoculated with 8.0 × 10 5, 1.6 × 10 6, 5.0 × 10 6 or 1.0 × 10 7 sporulated oocytes of E. debliecki to determine its pathogenicity. Clinical coccidiosis or deaths did not result from infections. Infections were confined to the jejunum and occasionally the duodenum. Microscopic lesions of mild to moderate villous atrophy were observed in one nursing pig given 5.0 × 10 6 oocytes and three weaned pigs given 1.6 × 10 6, 5.0 × 10 6 and 1.0 × 10 7 oocytes and examined 5 days post-inoculation. Pathogenic bacteria or viruses were not demonstrated in any pigs. Results of this study indicate that E. debliecki is not a cause of neonatal or wearing diarrhea in pigs.

Secretory diarrhea with protein-losing enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia, and congenital hepatic fibrosis: A new syndrome

Four infants had noninfectious intractable diarrhea, vomiting, anasarca, hepatomegaly, hypoglycemia, and malnutrition within the first 3 months of life. Their parents originated from the same Northeastern part of Quebec, and consanguinity was found in two kindreds. Diarrhea was secretory in three infants (mean stool volume 87 ml/kg/day, Na+ 108 mEq/L, Cl- 85 mEq/L). Hypoalbuminemia (mean 2.0 gm/dl), present in all infants, appeared to be secondary to a protein-losing enteropathy, which was documented in two infants. Histologic examination of the upper small intestine showed only mild to moderate villous atrophy. The remarkable findings were those of cystic dilation of the crypts and acute inflammation of crypts and lamina propria, all of which were most prominent in the colon and terminal ileum; the changes were progressive over time. Mild lymphangiectasia was found in all of the patients. Congenital hepatic fibrosis, present in all, was associated in one patient with a nonfunctional multicystic kidney. Prolonged total parenteral nutrition, intravenously administered albumin, antisecretory agents, and antibiotics were unsuccessful in controlling the disease. Although a total colectomy was followed by a temporary decrease in stool output and normalization of serum albumin concentration in one infant, the patients died between 4 and 21 months of age.

Intestinal Malabsorption and Immunoglobulin Deficiency

Available evidence suggests that hypogammaglobulinemia, particularly immunoglobulin A (IgA) deficiency, may be associated with intestinal malabsorption and mild to moderate villous atrophy of the proximal jejunal mucosa.1-3We have encountered such a patient who responded favorably in turn to a gluten-free diet and to tetracycline hydrochloride therapy administered orally. The purpose of this report is to relate the clinical and immunological findings in this case to published data from other patients with malabsorption and documented immunoglobulin deficiencies. Methods For Special Studies The serological and tissue techniques, as well as the method used to quantify mucosal lymphoid cells employing cell density indices (CDI), have been reported.4The CDI are arbitrary units which represent cells per unit area of interstitium.4In the previous study of eight specimens of normal human rectal mucosa, the CDI (mean ± SE of the mean) for IgA-, IgM- and IgG-containing lymphoid cells were 80.14