Problems of differential diagnosis of lymphoma and celiac disease. A case report

An association between celiac disease and non-Hodgkin's lymphoma of the small intestine has been recognized for many years. Coeliac disease is characterized by an enteropathy sensitive to gluten, malabsorption of food and partial or total villous atrophy. Also malignant lymphoma may present with malabsorption and mucosal lesion similar to that found in coeliac patients. The diagnosis of lymphoma in coeliac patients can be extremely difficult because the presenting symptoms and histological lesion are similar, but the presence of a cluster of symptoms such as abdominal pain malabsorption, weight loss in patients older than 40 years with a history of poorly responsive coeliac disease should raise a suspicion of malignancy. We present a case of 55 year-old man with malignant lymphoma and coeliac disease surgically treated in our Institute for intestinal obstruction.     

Giardiasis in children with chronic diarrhea. Incidence, growth, clinical symptoms and changes in the small intestine

During a six-year period, 29 children (aged 0.7-13.5 years, mean 3.3 years) suffering from chronic diarrhoea due to giardiasis were studied. The incidence of this illness was 81 per 1,000,000 per year among children aged 0- < 7 years. According to growth charts, relative height and weight of the patients decreased significantly (both approximately 0.5 SD) from before the onset of diarrhoea to the time of diagnosis and subsequently increased up to the end of catch-up growth. Small intestinal mucosal specimens were studied. Two patients had severe villous atrophy, 8 moderate abnormalities, 6 only slight changes and 13 biopsies were normal. D-xylose or lactose malabsorption was detected in 25% of the patients. The lactose malabsorption was due to hereditary low lactase levels. None of the patients with a Danish ethnic background showed lactose malabsorption. D-xylose absorption and the relative weight loss of the patients correlated with the degree of mucosal damage. Patients with persistent diarrhoea (n = 19) were younger and had a shorter duration of diarrhoeal illness and a more significant weight reduction than those with intermittent diarrhoea (n = 10). However, the age at onset of symptoms was similar in the two groups (medians 1.3 years). Seven patients contracted the disease abroad. They all developed persistent diarrhoea and had a more severe course of the illness than those who acquired the disease in Denmark.     

Malabsorption syndromes

BACKGROUND/AIMS: Malabsorption syndromes commonly result from a pathological interference of the normal digestive process. There have been major advances in the last 4 years. The purpose of this review is to highlight in the form of a brief summary the most outstanding information available. METHODS: The review was performed based on a medical literature search using MEDLINE (1993-1997), bibliographic reviews of book chapters and review articles. As a consequence of the extensive information incorporated in the period and the limited scope of this review, the review will focus in three aspects: (1) an overview on some clinical aspects of malabsorption; (2) diseases in which predominates the disturbed mucosal phase of the digestive process, and (3) providing information on diagnostic testing regarding malabsorption. RESULTS: Major advances on celiac disease, Whipple's disease, giardiasis, tropical sprue, malabsorption of oligo- and disaccharides, vitamin B12 and bile salts are discussed. New aspects on diagnostic procedures for malabsorption are also presented. CONCLUSION: Although major advances have given a great support to the investigation of malabsorption, yet the syndrome remains a major diagnostic dilemma. Based on the limited availability of most diagnostic tests, a simple and practical diagnostic algorithm is presented.     

Intestinal suction biopsy in childhood of experiences during 1968-1975 (author's transl)

From 1968 to 1975 532 intestinal suction biopsies were obtained in 371 children and adolescents using the paediatric Watson capsule. The youngest patient was 2 months old; a 9 months old infant has the lowest body weight of 3 520 g. Mucosal specimens were mainly taken from the upper jejunum. The whole procedure mostly required not more than 30 minutes. No serious complications were seen. Due to technical troubles several attempts were ineffective; the rate of successful biopsies was 89%. The paediatric Watson capsule proved to be easy to handle, mostly reliable, and therefore very suitable for intestinal biopsy in childhood. The dissecting microscope and histological findings were classified into four groups: normal mucosa, slight, moderate and severe mucosal lesions. Severe lesions were almost only demonstrated in patients with coeliac disease: in the active phase, in the early phase of remission under gluten free diet and during gluten loading or normal diet respectively, furthermore in an infant with protracted diarrhoea and in a child with agammaglobulinemia. A flat mucosa is not pathognomonic for coeliac disease but a constant morphological attribute and conclusive for diagnosis. Moderate mucosal lesions were seen in the remission of coeliac disease or during gluten loading and in some cases with protracted diarrhoea of infancy and with chronic malabsorption of unknown origin, furthermore in a child with immunoglobulin deficiency and in another one with iron deficiency anemia. The examination with the dissecting microscope can be performed very easily and makes obvious a very exact diagnostic information which is completed by the histological examination.     

Alpha-chain disease in a non-Mediterranean climate. A case report

The clinical, biochemical, immunological and histopathological features in a patient with alpha-chain disease are described. The patient, a 20-year-old Coloured man, presented with severe steatorrhoea, malabsorption, abdominal pain and progressive general deterioration. An heterogeneous abnormal band with IgA immunochemical specificity was detected on electrophoresis of the patient's serum and urine. This protein was identified as free alpha-chain and was present in serum, urine, saliva and jejunal juice. A jejunal mucosal biopsy specimen showed distinctive appearances associated with alpha-chain disease. Bone marrow involvement was found and abnormal lymphoid cells were seen in the circulation together with an increased B lymphocyte population derived from bone marrow. This is the third South African patient with alpha-chain disease to be diagnosed. The patient has shown a partial remission after 12 months' chemotherapy. There was rapid symptomatic response and normalisation of protein parameters which were not paralleled by an objectively discernible response as assessed by haematological examination, intestinal absorption studies and histology of the jejunal mucosa.     

Simultaneous presentation of autoimmune thyroiditis and celiac disease in an adult

Celiac disease may be associated with other underlying autoimmune diseases. Among these, thyroid disease has been described in around 10% of the cases with hypothyroidism being the most frequently reported. Clinical suspicion of thyroid involvement in patients with celiac disease is difficult since the symptomatology is scarce or is masked by the picture of malabsorption. Nonetheless, its detection is important since it is not solved by gluten free diet and its correction requires specific treatment. Thyroid function studies, in addition to determination of antithyroglobulin and antimicrosomal antibodies, should be considered in celiac patients refractory to conventional dietetic treatment. We herein present the case of a 65-year-old woman who consulted for a malabsorption syndrome in whom celiac disease of the adult was simultaneously presented with hyperthyroidism secondary to autoimmune thyroiditis.     

Magnetic resonance imaging in a case of Wernicke's encephalopathy

Wernicke's encephalopathy is an uncommon disorder caused by a thiamine deficiency which is clinically characterized by the triad of ophthalmoplegia, ataxia and disturbances of consciousness, each finding being variably present. The disease is caused by malnutrition or malabsorption, and is often associated with prolonged alcohol intake, neoplasm and extensive inflammatory processes of the digestive tract and parenteral hyperalimentation-induced gastrointestinal mucosal atrophy. Clinical diagnosis can be elusive and MRI may be the only imaging technique able to detect the cerebral lesions, whose type and distribution are characteristic of the Wernicke's encephalopathy, whereas CT is positive only in exceptional cases. We report a case of a 56-year-old woman who developed a Wernicke's encephalopathy 1 month after a colonic resection with signal intensity changes located in the mammillary bodies and in the medial thalamic nuclei.     

Renal allograft rejection: the temporal relationship and predictive value of plasma TNF (alpha and beta), IFN-gamma and soluble ICAM-1

Eosinophilic gastroenteropathy is an uncommon, idiopathic disease in children that is characterized by eosinophilic inflammation of the intestine. Predominant involvement of the mucosa is associated with diarrhea and less commonly gastrointestinal protein and fat malabsorption. A seven-year-old female was diagnosed with eosinophilic gastroenteritis. This condition was proven by biopsies attained through an endoscope. The most common symptoms were abdominal pain, diarrhea and edema. The patient had no eosinophilia. Her serum immunoglobulin E level was increased (1590 mg/dl). Barium studies revealed mucosal thickening of the antrum, distal jejunum and proximal ileum and prominent mucosal folds of the colon. Ultrasound examination revealed thickening of the colonic wall. The patient was treated with prednisolone (2 mg/kg/day). The symptoms subsided and serum immunoglobulin E decreased to 500 mg/dl 45 days later. The patient is being followed with a small maintenance dose of prednisolone with no relapse.     

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT

BACKGROUND: Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease. OBJECTIVE: To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease. DESIGN: Parallel study. SETTING: Two hospital outpatient clinics. PARTICIPANTS: 12 healthy volunteers, 12 patients with asymptomatic HIV disease, 12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV disease and diarrhea. MEASUREMENTS: Drug plasma concentrations were measured over 24 hours on day 4 of concurrent therapy. INTERVENTION: Oral isoniazid (300 mg/d), rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d). RESULTS: Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug exposure to isoniazid was lower in patients with diarrhea. CONCLUSIONS: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.     

Intestinal absorption in Saudi Arabia: an evaluation of the one hour blood xylose test

The screening value of the one-hour blood xylose test, corrected for body surface area, was prospectively studied in Saudi Arabian adults and children under investigation for suspected intestinal malabsorption. Sensitivity of discrimination between patients with and without upper small bowel disease was 91%, compared to 85% for the five-hour urine xylose test. Primary small bowel disorder was rare. In a three-year review, no cases of adult coeliac disease or tropical sprue were found. The most common causes of malabsorption were intestinal tuberculosis, abdominal lymphoma and immunoproliferative small intestinal disease. Despite its acceptability as an index of proximal small bowel function, the blood xylose test alone is an inadequate screening test for any of these conditions.     

Impact of Streptococcus pneumoniae bacteremia and human immunodeficiency virus type 1 on oral mucosal immunity

To determine whether defects in mucosal immunity were associated with invasive disease caused by a mucosal pathogen, Streptococcus pneumoniae, levels of salivary immunoglobulins and nonspecific immune factors were compared in subjects with human immunodeficiency virus type 1 (HIV-1) infection and in HIV-1-seronegative subjects with and without pneumococcal bacteremia. The IgA2 subclass may be of particular importance because S. pneumoniae produces IgA1 protease, which cleaves IgA1 but not IgA2. Levels (37-56 micrograms/mL) and proportions (11%-17%) of IgA2 were similar among groups. Serotype-specific capsular salivary IgA was present in a minority of patients with acute bacteremia. Levels of lactoferrin were increased with bacteremia. Neither selective mucosal IgA2 deficiency nor impaired nonspecific upper respiratory mucosal responses were associated with invasive pneumococcal disease during HIV-1 infection; thus, other defects in mucosal cellular responses and systemic immunity may predispose HIV-1-infected patients to invasive pneumococcal disease.     

Identification of tissue transglutaminase as the autoantigen of celiac disease

Celiac disease is characterized by small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption. In addition to nutrient deficiencies, prolonged celiac disease is associated with an increased risk for malignancy, especially intestinal T-cell lymphoma. Celiac disease is precipitated by ingestion of the protein gliadin, a component of wheat gluten, and usually resolves on its withdrawal. Gliadin initiates mucosal damage which involves an immunological process in individuals with a genetic predisposition. However, the mechanism responsible for the small intestinal damage characteristic of celiac disease is still under debate. Small intestinal biopsy with the demonstration of a flat mucosa which is reversed on a gluten-free diet is considered the main approach for diagnosis of classical celiac disease. In addition, IgA antibodies against gliadin and endomysium, a structure of the smooth muscle connective tissue, are valuable tools for the detection of patients with celiac disease and for therapy control. Incidence rates of childhood celiac disease range from 1:300 in Western Ireland to 1:4700 in other European countries, and subclinical cases detected by serological screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively. IgA antibodies to endomysium are particularly specific indicators of celiac disease, suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease. However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tissue transglutaminase as the unknown endomysial autoantigen. Interestingly, gliadin is a preferred substrate for this enzyme, giving rise to novel antigenic epitopes.     

Hyperoxaluriaas a complication of intestinal diseases (author's transl)

Urinary oxalate excretion was measured in healthy persons and patients with Crohn's disease, colitis ulcerosa, sprue and other diseases accompanied with malabsorption, and patients with insufficiency of the exocrine pancreas gland. Further measurements were made in patients after resection of parts of the small intestine or the colon. We found a clear increase of urinary oxalate excretion in patients with resected parts of the small intestine, sprue or other malabsorption syndromes. In 4 patients with resected parts of small intestine or pancreas we even found urolithiasis. Urinary oxalate excretion correlated significantly with steatorrhoea and increased if larger parts of small intestine were resected. Increased resorption of oxalate from food causes increased urinary excretion. Details about the patho-mechanism of this increased excretion are not known yet; an important factor seems to be the reduced absorption of fat in the small intestine.     

Celiac disease: a review

Celiac disease is relatively rare in the United States and many of the facets of this complex disorder are not completely understood. In the gluten-sensitive individual, celiac disease is activated by ingestion of cereal glutens. An abnormal immune system response to dietary gluten causes damage to the small bowel mucosa, which results in nutrient malabsorption. When gluten is removed from the diet, malabsorption resolves. Nursing intervention in celiac disease requires careful nutritional assessment and dietary instruction.     

Coeliac disease

In coeliac disease there is an abnormality of the intestinal mucosa which is caused by ingesting gluten. The intestinal lesion affects predominantly the proximal small intestine and the ileum is either normal or less severely involved than the jejunum. In some cases adaptive changes occur in the ileum, producing enhanced absorption in that region when there is malabsorption in the jejunum. The characteristic absorptive abnormality in coeliac disease is therefore jejunal malabsorption and ileal hyperabsorption. When such a situitation develops it is possible that an indivisual with a flat jejunal mucosa may develop no symptoms of the disease, since the adaptive changes in the ileum compensate for the jejunal lesion. This may explain why in Western society there are probably more cases of coeliac disease undiagnosed in the community that have been treated by their doctors. The basic lesion in coeliac disease appears to be genetically determined and it is likely to be a failure to clear antigen which normally enters the lamina propria of the gut resulting in the formation of immune complexes with complement fixation at gut level.     

Effect of fluvastatin sodium (XU62-320), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the induction of low-density lipoprotein receptor in HepG2 cells

Twelve patients with rheumatoid arthritis treated for at least 12 months with methotrexate and 11 matched rheumatoid arthritis controls underwent a standard d-xylose absorption test. No patients had any pre-existing clinical of biochemical evidence of malabsorption. No significant difference was observed in the 1 hour plasma d-xylose estimation between methotrexate treated patients and controls. The 2 to 5 hour urinary excretion ratio, however, was significantly lower in the methotrexate-treated group compared with controls indicating a minor degree of malabsorption. Six of the methotrexate treated patients and 5 of the controls underwent endoscopic duodenal biopsy but neither group demonstrated any significant histological changes. In conclusion, methotrexate therapy in patients with rheumatoid arthritis produces mild intestinal malabsorption.     

European Congress of Radiology (ECR), European Association of Radiology (EAR), European Society of Radiology (ESR): European Radiology between the past and the future

OBJECTIVE: To screen patients with SLE for malabsorption. METHODS: Twenty-one patients fulfilling the American College of Rheumatology (ACR) criteria for SLE were enrolled in the study. Patients were screened for malabsorption by the D-Xylose test (DXT) and by microscopic examination of the stool for fat droplets. All patients underwent upper GI endoscopy with biopsy from the second portion of the duodenum. The specimen was examined for morphologic abnormalities and for the presence of IgG, IgM, IgA, and kappa and lambda light chains. Ten patients without SLE served as controls. RESULTS: A history of abdominal pain and occasional diarrhea was elicited in 2/21 patients. These patients were found to have an abnormal DXT and excessive fecal fat excretion. In one of these patients, histologic examination revealed flattened and deformed villi with an inflammatory infiltrate. Two other patients showed isolated excessive fecal fat excretion with a normal microscopic appearance of the mucosa. In 20/21 patients the small bowel histology was normal. In all patients, immunoperoxidase staining revealed a normal quantity and distribution of the immunoglobulins and light chains within the intestinal mucosa. No correlation was demonstrated between CH50, C3, C4, anti-dsDNA levels and the malabsorption. CONCLUSION: In this series of SLE patients, the prevalence of malabsorption was 9.5%, and was even higher if isolated fat malabsorption was considered. A search for malabsorption in patients with SLE, and in particular in those with abdominal complaints, is recommended. The pathogenesis is not yet clear and warrants further investigation.     

Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators

BACKGROUND: Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition. AIM: To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine. METHOD: Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed. RESULTS: Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3-12.6). Their median daily faecal weight was 285 g (range 85-676) and median faecal fat output was 17 mmol/24 h (range 8.3-38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea. CONCLUSIONS: Idiopathic bile acid malabsorption, once suspected, especially by documenting true 'large volume' watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.     

Effect of chronic duodenal ulceration and its treatment with lanzoprazole or sucralfate on gastroduodenal mucosal protein turnover and TGF-alpha, bFGF, and EGF receptor expression in humans

In order to investigate whether chronic duodenal ulcer disease is a consequence of disturbed mucosal turnover and growth factor expression, we studied 16 patients with duodenal ulcers before, during, and after endoscopic healing with lansoprazole or sucralfate. Before treatment, gastric fundal and antral mucosal protein turnover rates were higher in patients than controls, without parallel increases in growth factors. Both forms of therapy produced similar changes, with overall increases in duodenal mucosal turnover and transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGF-r) levels. Measurements after healing showed persistent elevations of mucosal turnover in the antrum and duodenum and depressions of basic fibroblast growth factor (bFGF) in gastric fundal and duodenal mucosa. We conclude that mucosal turnover is abnormally high in patients with chronic duodenal ulcer disease and is not easily explained by growth factor changes. The failure of lansoprazole and sucralfate to normalize rates, despite endoscopic healing, may explain the high ulcer relapse rates in non-HP-eradicated patients.     

Gastrointestinal lesions in liver cirrhosis

The gastrointestinal bleeding commonly observed in patients with liver cirrhosis is usually from esophageal and gastric varices, gastroduodenal ulcer, and congestive gastropathy. Portal hypertension is the major causative factor of pathogenesis of GI lesions. In the present review, we focus in gastric mucosal defense and Helicobacter pylori infection in liver cirrhosis. Gastric mucosal defense is reduced in liver cirrhosis, especially prostaglandins which play a role in the gastric mucosal defense decreased in the gastric mucosal of patients with liver cirrhosis and rat portal hypertension model. Although H. pylori is strongly associated with peptic ulcer disease and chronic gastritis, several studies showed no relationship between H. pylori infection and gastroduodenal ulcer or the infection and congestive gastropathy in liver cirrhosis. Reduced gastric mucosal defense may account for the pathogenesis of GI lesions in liver cirrhosis.