Tropical Sprue 

Updated: Dec 15, 2014
Author: Rohan C Clarke, MD; Chief Editor: Julian Katz, MD 

Overview

Background

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. 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 2 different substances when other causes are excluded.

Tropical sprue (H&E, orig. mag. ×10). Tropical sprue (H&E, orig. mag. ×10).
Endoscopic views of unsuspected celiac disease. A: Endoscopic views of unsuspected celiac disease. A: Absent duodenal folds. B: Mucosal fissures and scalloped folds. C: Scalloped fold.

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.

Pathophysiology

The exact role of microbial agents in the initiation and propagation of the disease is poorly understood. 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.[1, 2, 3, 4]

Epidemiology

Frequency

United States

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

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.

Mortality/Morbidity

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 also lead to death, but this usually occurs in patients with comorbid conditions.

Race

Tropical sprue is confined to geographic regions, but it is observed in individuals of all races who live in or visit those regions.

Sex

The male-to-female ratio is equal.

Age

Tropical sprue is primarily an adult disease, but it has been described in children.

 

Presentation

History

See the list below:

  • 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:

    • Diarrhea

    • Weight loss

    • Leg swelling

    • Fatigue

    • Fever

Physical

See the list below:

  • Examination may reveal the following:

    • Weight loss

    • Dehydration

    • Pallor

    • Oral mucosa changes (glossitis, stomatitis)

    • Edema

  • Consider specific causes of diarrhea and malabsorption.

  • Consider the diagnosis of tropical sprue if the initial history, physical, and laboratory workups are suggestive of mucosal malabsorption.

  • Although tropical sprue can manifest as an acute diarrheal illness, the clinical diagnosis is usually not considered until patients present with chronic symptoms.

  • Diarrhea and fat malabsorption may occasionally be difficult to differentiate. Perform a 24- to 72-hour stool test for fat. Total stool fat less than 6-7 g/d excludes steatorrhea; therefore, consider chronic diarrhea.

Causes

See the list below:

  • Environmental

  • Residence or travel in an endemic tropical area

 

DDx

Diagnostic Considerations

Brown et al compared the histologic changes found in tropical sprue with those occurring in gluten-sensitive enteropathy, a condition for which tropical sprue is often mistaken. The study, which involved 12 patients with tropical sprue and 150 cases of gluten-sensitive enteropathy, identified no complete villous blunting in the duodenal mucosa of the tropical sprue patients, although partial blunting occurred in 75% of them. In contrast, complete villous blunting was identified in 25% of gluten-sensitive enteropathy patients. The investigators also found that in the appropriate clinical context, tropical sprue is indicated by involvement of the terminal ileum, with greater inflammation and villous blunting than in the duodenum, and by the presence, in the lamina propria, of a conspicuous eosinophil infiltrate.[5]

A study of Indian adults by Ghoshal et al indicated that, in comparison with patients with tropical sprue, those with celiac disease tended to be younger (< 35 years), have a longer duration of diarrhea and a higher platelet count, and more often demonstrate villous atrophy (subtotal or partial).[6]

Diseases of general fat malabsorption to consider include the following:

  • Bacterial overgrowth

  • Ileal diseases

  • Pancreatic disorders

Mucosal diseases leading to malabsorption to consider include the following:

  • AIDS enteropathy

  • Celiac sprue

  • Cryptosporidia

  • Giardiasis

  • Infectious causes

  • Nonspecific enteropathy

  • Norwalk virus

  • Radiation enteropathy

  • Intestinal lymphoma

Differential Diagnoses

 

Workup

Laboratory Studies

See the list below:

  • Clinical presentation, including diarrhea, malabsorption of nutrients, and anemia workup, influences the extent of diagnostic tests. Findings of steatorrhea, mucosal malabsorption of 2 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.

  • CBC count: This shows megaloblastic anemia associated with reduced folate and vitamin B-12 levels in as many as 60% of patients.

  • Blood chemistry test: This includes potassium, calcium, magnesium, phosphate, albumin, cholesterol, and iron studies.

  • Stool collection test

    • This measures 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

    • For this study, 25 g D-xylose is administered orally.

    • 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.

Imaging Studies

See the list below:

  • 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.

  • Use of esophagoduodenoscopy may reveal subtle or dramatic mucosal changes,[7] as seen in the following images.

    Endoscopic views of unsuspected celiac disease. A: Endoscopic views of unsuspected celiac disease. A: Absent duodenal folds. B: Mucosal fissures and scalloped folds. C: Scalloped fold.

Other Tests

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 of13 C-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.[8] The investigators simultaneously performed intestinal permeability measurements with the lactulose/rhamnose (L/R) ratio on a timed 90-minute blood test with the13 C-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%).[8] 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 the13 C-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."[8] The investigators believe the13 C-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."[8]

Procedures

See the list below:

  • Jejunal biopsy

    • Mild villous atrophy

    • Increased villous crypts and mononuclear cellular infiltrates, enlarged epithelial cells, and large nuclei caused by folate and/or vitamin B-12 deficiency

  • Characteristic accumulation of lipid beneath the basement membrane

Histologic Findings

The following images are supportive of histopathologic findings of tropical sprue.[9]

Subtotal villous atrophy (H&E, orig. mag. ×10). Subtotal villous atrophy (H&E, orig. mag. ×10).
Tropical sprue (H&E, orig. mag. ×10). Tropical sprue (H&E, orig. mag. ×10).
 

Treatment

Medical Care

See the list below:

  • Patients with tropical sprue rarely present to the 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

  • 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.

  • Assess patients' responses by improvement of symptoms, weight gain, and correction of anemia. The duration of treatment depends on the duration of symptoms.

 

Medication

Medication Summary

Nutrient replacement to correct deficiencies in patients with tropical sprue often includes folic acid, vitamin B-12, and iron. Antibiotic therapy is also helpful because early eradication of bacterial pathogens can relieve continuing injury to the gut.

Vitamins

Class Summary

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.

Folic acid (Folvite)

Water-soluble vitamin used in nucleic acid synthesis. Required for normal erythropoiesis. Typically 5 mg po daily. Corrects megaloblastic anemia resulting from folate deficiency and helps regeneration of intestinal mucosa.

Cyanocobalamin (Vitamin B-12, Crystamine, Cyomin)

Water-soluble vitamin essential for normal erythropoiesis. Required for healthy neuronal functions and normal functions of rapidly growing cells. Typically 1000 mcg IM weekly.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Tetracycline (Sumycin)

This and oxytetracycline are bacteriostatic antibiotics that inhibit protein synthesis of bacteria. Usually 250 mg po four times daily for up to four months.

Minerals

Class Summary

Patients with anemia may need iron replacement along with folic acid and vitamin B-12.

Iron sulfate (Ferrous sulfate, Feosol)

Nutritionally essential inorganic substance.

 

Follow-up

Further Outpatient Care

See the list below:

  • 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 CBC count and electrolytes at least monthly.

  • Correct folate, vitamin B-12, and any other deficiencies.

Further Inpatient Care

See the list below:

  • Patients with tropical sprue are not usually admitted as inpatients unless they present with at 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).

Inpatient & Outpatient Medications

See the list below:

  • The same medications are used in both outpatient and inpatient settings (see Medication).

Deterrence/Prevention

See the list below:

  • No direct evidence indicates that antibiotic prophylaxis can prevent tropical sprue.

Complications

See the list below:

  • Anemia

  • Malnutrition

  • Vitamin deficiency

Prognosis

See the list below:

  • Prognosis of this condition is generally good.

Patient Education

See the list below:

  • 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 Esophagus, Stomach, and Intestine Center, as well as Traveler's Diarrhea.