Practical Approach to the Flattened Duodenal Biopsy.

Celiac disease features duodenal intraepithelial lymphocytosis with or without villous atrophy. Lymphocytosis without villous atrophy will be proven to represent celiac disease in 10% to 20% of cases. The differential diagnosis is broad: Helicobacter pylori gastritis, NSAID injury and bacterial overgrowth are considerations. Lymphocytosis with villous atrophy is very likely to be celiac disease, but there are mimics to consider, including collagenous sprue, tropical sprue, drug injury, and common variable immunodeficiency. Histologic clues to a diagnosis other than celiac disease include paucity of plasma cells, excess of neutrophils, granulomas, and relative paucity of intraepithelial lymphocytes.

Prevalence and Characteristics of Duodenal Villous Atrophy in Renal Transplant Patients Presenting With Persistent Diarrhea in a Developing Country.

OBJECTIVES: Persistent diarrhea is a common complication after solid-organ transplant, including kidney transplant. Data on duodenal villous atrophy as a cause of persistent diarrhea in renal transplant recipients are scarce. MATERIALS AND METHODS: We conducted a prospective analysis of 207 patients who received renal transplants from 2009 to 2012 with persistent diarrhea and who underwent upper gastrointestinal endoscopy and duodenal biopsies. Duodenal biopsies were examined for duodenal villous atrophy. Age, sex, transplant duration, and drugs were compared between patients with and without duodenal villous atrophy. After exclusion of known causes of duodenal villous atrophy, a 3-month course of antibiotics was given and outcomes were analyzed. RESULTS: Of 207 renal transplant recipients, 104 patients (49.8%) displayed duodenal villous atrophy. Of these, 92 (88.5%) were male patients. The mean age of patients with duodenal villous atrophy was 34.9 ± 10.3 years. The mean onset of persistent diarrhea in DVA-positive patients posttransplant was 2.16 ± 0.8 years. Celiac disease serology was positive in 18 (17.3) patients. Giardiasis was demonstrated in 11 patients (10.7%), whereas immunoproliferative small intestinal disease was shown in 7 patients (6.8%). The remaining 68 patients (65.38%) received antibiotics, with 50 recipients (74.6%) showing complete response, although 13 of these patients (26%) relapsed. Among the remaining 18 patients (26.47%), 9 (50%) had other causes and 9 (50%) had no cause found. Isoniazid prophylaxis showed statistically significant negative association with duodenal villous atrophy. CONCLUSIONS: Duodenal villous atrophy is highly prevalent in renal transplant recipients irrespective of age, sex, and posttransplant duration. We found tropical sprue, giardiasis, immunoproliferative small intestinal disease, and celiac disease to be important causes of duodenal villous atrophy. Therefore, duodenal biopsy is recommended in renal transplant recipients with persistent diarrhea.

Chronic infections of the small intestine.

PURPOSE OF REVIEW: Chronic infections of the small intestine cause significant morbidity and mortality globally. This review focuses on the recent advances in the field of our understanding of selected intestinal infections. RECENT FINDINGS: Primary and secondary immunodeficiency increase the susceptibility to many chronic intestinal infections. Endoscopy and intestinal biopsies are central to establishing a diagnosis of these conditions. Tuberculosis (TB) remains a major global health challenge. Emerging therapeutic agents to counteract multidrug-resistant strains have shown clinical efficacy, but concerns regarding mortality remain. PCR-based diagnostic TB tests have the potential to reduce diagnostic delays, but remain to be validated for intestinal infections. Adjunctive diagnostic imaging modalities can differentiate infections from Crohn's disease with increasing accuracy. Whipple's disease remains rare, but there have been substantial advances in our understanding of the causative organism Tropheryma whipplei. Extended treatment with broad-spectrum antibiotics is effective in most cases. The narrow therapeutic window and limited armamentarium for treating invasive filamentous fungal infections contribute to their significant morbidity and high rates of mortality. SUMMARY: The speed and accuracy of diagnosing chronic intestinal infections have improved with recent imaging and laboratory methodologies. Significant research opportunities remain for clinicians and scientists to improve the diagnostic accuracy and clinical outcomes of chronic intestinal infections.

A presentation of latent tropical sprue in a Canadian hospital.

Tropical sprue (TS) is a chronic diarrheal disease of unknown etiology characterized by malabsorption and small bowel mucosal abnormalities. TS affects residents of, and visitors to, endemic tropical regions. Rarely the disease may remain latent for several years, and to date, few cases of latent TS have been reported in Europe or North America. However, in our increasingly multicultural communities and in a 'global village' where travel is common, clinicians must maintain a high index of suspicion for TS in patients presenting with diarrhea and malabsorption who have traveled to endemic regions. TS may mimic common diarrheal diseases that are seen in developed nations, including celiac disease, Crohn's disease, bacterial overgrowth, and other infectious etiologies. Accordingly, once these more common etiologies have been ruled out, TS must be considered in patients presenting with diarrhea after travel to endemic regions. We present a unique Canadian case of latent TS, with a brief review of the diagnostic approach and treatment.

Current spectrum of malabsorption syndrome in adults in India.

AIM: Tropical sprue was considered to be the most important cause of malabsorption in adults in India. However, several reports indicate that celiac disease is now recognized more frequently. METHODS: We analyzed the clinical presentation, endoscopic and histological features of 94 consecutive patients (age >12 years) with chronic diarrhea and malabsorption syndrome. The spectrum of disease in these patients and features differentiating celiac disease and tropical sprue are reported here. RESULTS: Celiac disease (n = 61, 65%) was the most common cause of malabsorption followed by tropical sprue (21, 22%). Other conditions including cyclosporiasis (3), Crohn's disease (2), common variable immunodeficiency (2), lymphangiectasia (1), William's syndrome (1), and idiopathic malabsorption (3) accounted for the remainder. A greater number (21, 34%) of patients with celiac disease than those with tropical sprue (4, 19%) presented with atypical manifestations. Patients with celiac disease were younger (p = 0.001), more often had anemia, (p = 0.001), scalloping of folds (p = 0.001), moderate (p = 0.02) or severe (p = 0.001) villous atrophy, higher grade of intraepithelial lymphocytic infiltration (p = 0.001), crypt hyperplasia (p = 0.001), cuboidal (p = 0.001) and pseudostratified (p = 0.009) surface epithelial cells, and diffuse (p = 0.001) epithelial damage. In comparison, patients with tropical sprue were older and more often had normal duodenal folds, normal villi, tall columnar epithelial cells and focal epithelial damage. CONCLUSIONS: Celiac disease was the most frequent cause of malabsorption syndrome in this series of patients. There are significant clinical and histological differences between celiac disease and tropical sprue.

Diagnostic value of endoscopy for the diagnosis of giardiasis and other intestinal diseases in patients with persistent diarrhea from tropical or subtropical areas.

OBJECTIVE: Upper endoscopy has been suggested as a valuable tool in the diagnosis of giardiasis. The aim of this study was to compare two methods based on endoscopy, i.e. microscopy of duodenal fluid and histology, with a fluorescent-antibody assay for the detection of Giardia lamblia cysts in stool specimens. The role of endoscopy in the identification of other causes of chronic diarrhea acquired during travel abroad was also evaluated. MATERIAL AND METHODS: Thirty-one patients (9 F, 22 M, median age 39 years, range 19-63 years) with persistent diarrhea after returning from tropical or subtropical areas agreed to undergo upper gastrointestinal endoscopy before and after treatment. Lower gastrointestinal endoscopy was subsequently performed. Three stool samples from each patient were examined using the direct fluorescent-antibody assay (DFA) for the detection of G. lamblia, and by routine methods for other protozoal and bacterial enteric pathogens. Each patient underwent upper endoscopy and biopsies and duodenal fluid samples were taken. In 12 patients a further lower endoscopy was performed. RESULTS: In 16 patients G. lamblia was detected in stool samples by DFA (relative sensitivity: 100%). Histology of duodenal biopsies and microscopy of duodenal fluids allowed diagnosis of giardiasis to be made in only 8, and 3 patients, respectively (relative sensitivities: 21% and 44%). Besides giardiasis, upper endoscopic examination revealed an alternative diagnosis (tropical sprue), whereas six additional diagnoses were made by colonoscopy. In six patients the cause of chronic diarrhea remained unclear. CONCLUSIONS: Compared to stool examinations using DFA, upper endoscopy is less sensitive for the diagnosis of giardiasis. In patients with negative stool examinations, lower endoscopy yields relevant diagnoses more often than upper endoscopy.

[Fever of unknown origin in the 21st century: infectious diseases]. / Fieber unklarer Genese im 21. Jahrhundert. Teil 1: Infektionskrankheiten.

Fever of unknown origin (FUO) is a rare but important disease. The definition of FUO has not changed in the last 50 years. Classical FUO is defined by an illness of at least 3 weeks duration with fever greater than 38 masculine C, and no established diagnosis after 1 week of hospital investigation. The causes of FUO can be divided in four categories: infectious diseases, noninfectious inflammatory diseases, neoplasms, and others (miscellaneous). Recent studies have surprisingly shown that despite improved diagnostic procedures the percentage of patients with FUO, in which no diagnosis after intensive investigations in specialized centres can be found, has increased. However, finding the correct diagnosis in FUO is essential for these patients for psychological and vital reasons. Therefore and because of economic reasons patients with FUO should be investigated in specialized centres with a department for rheumatology and infectious diseases.

Persistent diarrhea in the returning traveler: think beyond persistent infection.

The report describes a young female United Nations worker, stationed in East Timor for an extended duration, who presented with persistent travelers' diarrhea and who was convinced that she was harboring a persistent infestation. In fact, careful history, laboratory evaluation and endoscopy with duodenal biopsies found all the classical hallmarks of unmasked celiac sprue. The patient then had a dramatic response to a gluten-free diet, with complete resolution of symptoms. Persistent travelers' diarrhea is an entity which carries an interesting and extensive differential diagnosis beyond persistent enteric infections or infestations. Rather, many sufferers have long been cleared of the initial offending pathogen and are left with either a post-infectious disorder of absorption, digestion, motility or visceral sensation or carry a chronic gastrointestinal disorder which has been unmasked by an enteric infection, such as idiopathic inflammatory bowel disease, gastrointestinal malignancy or celiac sprue. Other key issues raised by the case include the vanishing incidence of tropical sprue, an entity to which most clinicians would have mistakenly attributed this malabsorptive syndrome arising in a traveler, and the under-recognition of the protean manifestations of celiac sprue, to which we would add persistent travelers' diarrhea.

Tropical sprue: revisited.

OBJECTIVE: To review the experience of patients presenting with clinical manifestations of tropical sprue and assess their diagnosis and management, response to treatment and follow up. METHODS: This single center retrospective descriptive study was done at Shifa International Hospital, Islamabad from January 1994 to January 2003. All patients who presented with diarrhea, anorexia, weight loss and anemia and who proved to have partial villous atrophy on intestinal biopsy and had responded to treatment with antibiotic and folic acid,were included in this review. RESULTS: A total of 42 patients were encountered during these years. There were 31 (74.0%) males and 11 (26%) females. The age ranged from 17-66 years. All patients presented with diarrhea, weight loss, anorexia and had megaloblastic anemia. In all patients, a distal duodenal biopsy showed partial villous atrophy. All were treated with tetracycline 1 g per day and folic acid 5 mg per day and responded to treatment within 4 weeks. Total treatment lasted 3 months and resulted in complete resolution of symptoms and gain of weight. The follow up lasted for a mean of 5 years and no relapses were noted. CONCLUSION: Tropical sprue presents with diarrhea, anorexia, weight loss, and megaloblastic anemia. The partial villous atrophy has been a constant finding. The response to treatment to tetracycline and folic acid has been uniformly successful.

[Chronic diarrhea after a journey to Sri Lanka]. / Chronische Diarrhö nach Aufenthalt in Sri-Lanka.

A 51-year-old woman was referred for evaluation of chronic diarrhea. She had spent a 14 day vacation in Sri Lanka three years ago. The clinical examination of the patient was unremarkable. Values for protein, iron, zinc, copper and folic acid were decreased and the Shilling- and D-xylose tests revealed pathological results. Gliadin and Endomysium antibodies were not detectable. Histologic examination of the duodenum displayed chronic duodenitis with increased epithelial regeneration and villous atrophy. In the MRI a segment of the mid small bowel with increased thickness of the intestinal wall was described. Abdominal CT-scans demonstrated multiple, enlarged mesenteric lymph nodes. Laparoscopy with biopsies of the ileum and mesenteric lymph nodes excluded a malignant lymphoma, mycobacteriosis or Whipple's disease. Oral therapy with tetracyclines (250 mg q. i. d.) and substitution of folic acid and iron led to rapid improvement of the clinical symptoms which persisted after cessation of the antibiotic therapy. In view of the clinical course tropical sprue has to be assumed despite the short duration of the journey to a tropical region.

[Tropical sprue as the cause of chronic diarrhea after travel to Southeast Asia]. / Tropische Sprue als Ursache einer chronischen Diarrhö nach Südostasienreise.

A 43-year-old woman developed abdominal pain and diarrhea following a travel to Malaysia. Examinations in another hospital proved no evidence of infection, an empirical antibiotic therapy with ciprofloxacin yielded no benefit. One and a half year later, the patient was admitted to our department because of persistent diarrhea and wasting. Laboratory tests showed megaloblastic anemia, folate deficiency and steatorrhea. Stool specimens for bacterial pathogens and parasites were negative. Endoscopy and biopsy from the distal portion of the duodenum revealed broadening and shortening of the villi and an increased infiltration of the lamina propria by chronic inflammatory cells (plasma cells and lymphocytes). In conclusion, diagnosis of tropical sprue was established. The therapy comprised of tetracycline for six weeks and folic acid for six months. Subsequently, the diarrhea disappeared, the patient continuously gained weight and was free of any complaints. The complete remission following this regimen proved the suspected diagnosis. Differential diagnosis in any patient who recently returned from the tropics may be a challenge. Tropical sprue predominantly occurs during or after a longer stay in endemic areas. However, if chronic diarrhea and signs of malabsorption develop after a short journey to India, South-East Asia and parts of the Caribbean, tropical sprue has to be considered, too.

[Tropical sprue]. / Esprue tropical.

We report the case of a 60 year old female who presented with diarrhoea and malabsorption syndrome, confirmed by the laboratory data and the radiologic examination, which developed after a journey to Egypt. The mainly finding was flattening of the villi in the jejunal biopsy; the syndrome recovered after treatment with antibiotics and folic acid. The case fulfills the diagnostic criteria of tropical sprue although this country is not considered as an endemic area.

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.

[Tropical sprue. Apropos of a case observed in the Paris region]. / La sprue tropicale. A propos d'un cas observé en région parisienne.

A case of tropical sprue in a 73-year old parisian male returning from endemic areas is reported. Clinical manifestations were megaloblastic anemia, malabsorption and protein-losing enteropathy. Biopsy of the jejunal mucosa showed partial villous atrophy with thickening of the basement membrane region; fat droplets were observed inside and close to the epithelial cells on electron microscopy study. Fat intestinal absorption after a test meal was delayed. Clinical, biological and histological improvement was obtained with tetracycline and folic acid therapy. The particular clinical and anatomical features of this case, as well as the difficulties for establishing the diagnosis of tropical sprue in non-endemic areas are analyzed.

Mala absorción tropical en Bogotá / Tropical malabsorption in Bogota

Se presentan 75 casos de mala absorción tropical, 65 adultos y 10 niños, estudiados desde el año de 1968 en el Hospital San Juan de Dios de Bogotá. La mayoría de los pacientes provenían de Cundinamarca y del Distrito Especial de Bogotá. En todos hubo mala absorción de la D-xilosa y esteatorrea. La biopsia peroral de la mucosa intestinal practicada en 64, mostró atrofia de 1+ en 16, de 2+ en 30, de 3+ en 18 y en ninguno se observó atrofia de 4+. Se encontró anemia en 58 pacientes, la cual fue de tipo megaloblástico en 45 (60 por ciento), ocasionada a su vez por deficiencia de ácido fólico, en 4, de Vitamina B12 en 9 y de ácido fólico y Vitamina B12 en 32. Fueron hallazgos frecuentes además del peso bajo, la glositis, la carotinemia baja (<40ug/dl) la colesterolemia inferior a 150mg/dl y la albuminemia por debajo de 3.5 g/dl. Fueron tratados exitosamente con dieta balanceada, ácido fólico, Vitamina B12, tetraciclina o sulfas, en forma aislada o empleando combinaciones de estos medicamentos. En presencia de megaloblastosis la terapia ideal es el tratamiento "triconjugado" de Vitamina B12, ácido fólico y tetraciclina; solamente falleció un paciente, por tromboembolismo pulmonar. El diagnóstico diferencial debe hacerse principalmente con la enteropatía por Gluten y con la anemia perniciosa