Tropical sprue (TS) is a syndrome characterized by acute or chronic diarrhea, weight loss, and malabsorption of nutrients. It occurs in residents of or visitors to the tropics and subtropics, and it may be caused by environmental factors.[1] The first description of tropical sprue is attributed to William Hillary's 1759 account of his observations of chronic diarrhea while in Barbados. Subsequently, tropical sprue was described in tropical climates throughout the world. The definition has been expanded to include malabsorption of at least two different substances when other causes are excluded.
View Image
Tropical Sprue. Tropical sprue (hematoxylin-eosin [H&E], original magnification ×10).
The exact causative factor of tropical sprue is unknown, but an intestinal microbial infection is believed to be the initiating insult. The infection results in enterocyte injury, intestinal stasis, and possible bacteria overgrowth. Villous destruction and demonstrable nutrient malabsorption occur in varying degrees. Folate, vitamin B-12, and iron deficiencies are the most common nutrient deficiencies.
Patient education
Travelers to the tropics should be aware of this syndrome and take steps to limit exposure to enteric pathogens. If protracted diarrhea occurs, early presentation to medical personnel is helpful.
For patient education resources, see the Digestive Disorders Center, as well as Diarrhea, Traveler's (Traveler's Diarrhea).
The exact role of microbial agents in the initiation and propagation of the disease is poorly understood.[1] One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury; then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit. Central to this process is folate deficiency, which probably contributes to further mucosal injury.
Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue. Enterocyte injury can cause these elevations. Enteroglucagon causes intestinal stasis, but the role of motilin is not clear.
The upper small intestine is predominantly affected; however, because it is a progressive and contiguous disease, the distal small intestine up to the terminal ileum may be involved. Pathological changes are rarely demonstrated in the stomach and colon. Coliform bacteria, such as Klebsiella, E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue.[2, 3, 4, 5]
Tropical sprue appears to be declining globally.[6]
United States data
Tropical sprue occurs in geographically limited areas. The syndrome is not reported in US patients unless they have lived in or traveled to any of the areas described below.
International data
Tropical sprue occurs in both epidemic and endemic forms, primarily in Southeast Asia and the Caribbean. The actual prevalence of the endemic form is difficult to estimate, but rates as high as 8% are reported in Puerto Rico. One unusual feature is that tropical sprue appears to be limited to certain geographic areas, even within the tropics. For example, although tropical sprue is commonly reported in Puerto Rico and the Dominican Republic, it is not reported in Jamaica. Only a few cases are reported in emigrants from southern Africa.
Race-, sex-, and age-related demographics
Tropical sprue is confined to geographic regions, but it is observed in individuals of all races who live in or visit those regions.
The male-to-female ratio is equal.
Tropical sprue is primarily an adult disease, but it has been described in children.
Prognosis is generally good for patients with tropical sprue.
Morbidity/mortality
Acute illness complicated by fluid and electrolyte deficits is rarely fatal. The frequency of this complication is not known but appears to be decreasing. Chronic illness with severe malabsorption and anemia can lead to death, but this usually occurs in patients with comorbid conditions.
Complications
Complications of tropical sprue include anemia, malnutrition, and vitamin deficiency.
Tropical sprue manifests clinically with a spectrum of signs and symptoms. It may develop in natives or travelers to the tropics, and it may not appear until as long as 10 years after the patient has left there. No definitive marker of tropical sprue exists; hence, these claims remain unsubstantiated. Patients may experience the following:
Steatorrhea
Diarrhea
Weight loss
Leg swelling
Abdominal swelling
Fatigue
Fever
Physical examination
Physical examination in patients with tropical sprue may reveal the following:
Clinical presentation, including diarrhea, malabsorption of nutrients, and anemia workup, influences the extent of diagnostic tests. Findings of steatorrhea, mucosal malabsorption of two substances (eg, fat, D-xylose), and villous atrophy (demonstrated by means of biopsy) are adequate to make a diagnosis. Response to treatment is considered by some to be the conclusive evidence that confirms the diagnosis.
Complete blood cell (CBC) count
The CBC shows megaloblastic anemia associated with reduced folate and vitamin B-12 levels in as many as 60% of patients.
Blood chemistry test
Blood chemistry studies include levels of potassium, calcium, magnesium, phosphate, albumin, and cholesterol, as well as iron studies.
Stool collection test
Stool collection is used to measure fat content over 72 hours on a diet of 80-100 g of fat. A result of more than 6 g in 24 hours is abnormal (positive for fat malabsorption). Fatty stools are usually observed when the stool fat content is 15 g or more.
D-Xylose absorption test
The D-xylose absorption test involves oral administratoin of 25 g D-xylose. In well-hydrated patients with normal renal function, abnormal results (ie, positive for mucosal malabsorption) include a 5-hour urine collection of less than 4 g and a 1-hour serum collection of less than 20 mg/dL.
13C Sucrose breath test
Another possible tool to determine gut health may be a noninvasive marker. In a small Australian study, Ritchie et al reported a novel use of of 13C-sucrose breath test in 36 Aboriginal and non-Aboriginal children to measure enterocyte sucrase activity as a marker of small intestinal villus integrity and function.[9] The investigators simultaneously performed intestinal permeability measurements with the lactulose/rhamnose (L/R) ratio on a timed 90-minute blood test with the 13C-sucrose breath test.
Findings included a significantly decreased absorption capacity in Aboriginal children with acute diarrhea (mean 1.9%; cumulative percentage calculated of dose recovered at 90 min) relative to Aboriginal children without diarrhea (4.1%) or non-Aboriginal children (6.1%).[9] The mean L/R ratio in the Aboriginal children with diarrhea was 31.8, whereas the nondiarrheal Aboriginal children's was 11.4.
Ritchie et al noted a significant inverse correlation between the13C-sucrose breath test and the L/R ratio and concluded the breath test discrimated "among Aboriginal children with diarrhea, asymptomatic Aboriginal children with an underlying environmental enteropathy, and healthy non-Aboriginal controls."[9] The investigators believe the 13C-sucrose breath test "provides a noninvasive, easy-to-use, integrated marker of the absorptive capacity and integrity of the small intestine and could be a valuable tool in evaluating the efficacy of interventions aimed at improving gut health."[9]
A barium swallow and follow-through may reveal increased caliber and thickening of mucosal folds or flocculation and segmentation of barium, depending on the type of barium used.
Esophagogastroduodenoscopy (EGD)
EGD may reveal subtle or dramatic mucosal changes of the duodenum and or jejunum,[10] as seen in the following images.
Jejunal biopsy findings include mild villous atrophy, as well as increased villous crypts and mononuclear cellular infiltrates, enlarged epithelial cells, and large nuclei caused by folate and/or vitamin B-12 deficiency. There is a characteristic accumulation of lipid beneath the basement membrane.
The following images are supportive of histopathologic findings of tropical sprue.[11]
View Image
Tropical Sprue. Subtotal villous atrophy (hematoxylin-eosin [H&E], original magnification ×10).
View Image
Tropical Sprue. Tropical sprue (hematoxylin-eosin [H&E], original magnification ×10).
Patients with tropical sprue are not usually admitted as inpatients unless they present with a diagnosis of chronic diarrhea or malabsorption with dehydration and weight loss (see Medical Care).
Patients admitted with suspected tropical sprue should undergo workup and evaluation as previously described (see Workup).
Patients with tropical sprue rarely present to the emergency department (ED) with the following symptoms. Unless folate or vitamin B-12 deficiencies are noted, the diagnosis will probably be made later. The symptoms require urgent evaluation and initiation replacement of deficient nutrients, fluid, and electrolytes. Hospital admission is indicated in complicated cases. Symptoms include the following:
Acute diarrhea
Volume depletion
Electrolyte imbalance
Symptomatic anemia
Leg swelling
Without treatment, tropical sprue runs a relapsing course and can result in severe malnutrition.
Useful therapeutic interventions involve antibiotics and replacement of nutrients (eg, folic acid, vitamin B-12, iron), deficient fluid, and sometimes blood. However, despite success reported in other regions, antibiotic therapy for tropical sprue is not useful in patient populations of southern India.
Generally, administer a combination of antibiotics and folic acid to patients for 3-6 months. Patients with symptoms persisting longer than 6 months may be administered the combination for as long as a year.
Tetracycline 250 mg po QID for up to 4 months.
Folic acid 5 mg po daily for up to four months
Assess patients' responses by improvement of symptoms, weight gain, and correction of the macrocytic anemia. The duration of treatment depends on the duration of symptoms. This is notable with regards to Vitamin B 12 1000 mcg IM injections weekly.
Observe patients regularly to ensure that they respond to treatment and that the correct diagnosis is made. The patient should be observed at least once a month with careful monitoring of lab studies to make sure that any signs or symptoms of malabsorption have been corrected.
Monitor weight gain.
Monitor the patient's complete blood cell (CBC) count and electrolytes at least monthly.
Correct folate, vitamin B-12, and any other deficiencies.
Nutrient replacement to correct deficiencies in patients with tropical sprue often includes folic acid, vitamin B-12, and iron. Prolonged antibiotic therapy is also helpful because early eradication of bacterial pathogens can relieve continuing injury to the gut.
No direct evidence indicates that antibiotic prophylaxis can prevent tropical sprue.
Clinical Context:
Folic acid is a water-soluble vitamin used in nucleic acid synthesis. It is required for normal erythropoiesis. The regimen is typically 5 mg PO daily. This corrects megaloblastic anemia resulting from folate deficiency and helps regeneration of intestinal mucosa.
Clinical Context:
Cyanocobalamin is a water-soluble vitamin essential for normal erythropoiesis. It is required for healthy neuronal functions and normal functions of rapidly growing cells. Typically, a regimen of 1000 mcg IM weekly is used.
Nutritionally essential organic substances used in metabolism. Used in nucleic acid synthesis, required for normal erythropoiesis, and help in regeneration of intestinal mucosa. Patients with tropical sprue commonly have deficiencies of folate and, sometimes, vitamin B-12.
Clinical Context:
Tetracycline and oxytetracycline are bacteriostatic antibiotics that inhibit protein synthesis of bacteria. The regimen is usually 250 mg PO four times daily for up to 4 months.
Rohan C Clarke, MD, Attending Physician, Department of Gastroenterology, JPS Health Systems Hospital
Disclosure: Nothing to disclose.
Coauthor(s)
Lisa Anne Ozick, MD, Attending Gastroenterologist, Leumit Health Clinic, Israel
Disclosure: Nothing to disclose.
Oluyinka S Adediji, MD, MBBS, Consulting Staff, Department of Adult and General Medicine, Health Services Incorporated, Montgomery, Alabama
Disclosure: Nothing to disclose.
Rachael M Ferraro, DO, Internal Medicine Hospitalist, Torrance Memorial Medical Center, Little Company of Mary Hospital
Disclosure: Nothing to disclose.
Sabo B Tanimu, MD, Fellow, Department of Medicine, Division of Gastroenterology, Harlem Hospital Center
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
Burt Cagir, MD, FACS, Associate Regional Dean and Professor of Surgery, Geisinger Commonwealth School of Medicine; Director, General Surgery Residency Program, Executive Director, Donald Guthrie Foundation for Research and Education, Guthrie Robert Packer Hospital; Medical Director, Guthrie/RPH Skills and Simulation Lab; Associate in Surgery, Guthrie Robert Packer Hospital and Corning Hospital
Disclosure: Nothing to disclose.
Additional Contributors
Manoop S Bhutani, MD, Professor, Co-Director, Center for Endoscopic Research, Training and Innovation (CERTAIN), Director, Center for Endoscopic Ultrasound, Department of Medicine, Division of Gastroenterology, University of Texas Medical Branch; Director, Endoscopic Research and Development, The University of Texas MD Anderson Cancer Center
Gorbach, SL, Banwell, JG, Jacobs, B, et al. Tropical Sprue and Malnutrition in West Bengal. I. Intestinal microflora and absorption. American Journal of Clinical Nutrition. 1970. 23:1545.
Klipstein, FA, Holdeman, LV, Corcino, JJ, et al. Enterotoxigenic intestinal bacteria in tropical sprue. Annals of Internal Medicine. 1973. 79:632.
){kind=link}
){kind=link}
){kind=link}