AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 TS is attributed to William Hillary's 1759 account of his observations of chronic diarrhea while in Barbados. Subsequently, TS 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.

The exact causative factor 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 TS. 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 are isolated and are the usual organisms associated with TS.

Frequency

United States

The syndrome occurs in geographically limited areas. TS is not reported in US patients unless they have lived in or traveled to any of the areas described below.

International

TS 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 TS appears to be limited to certain geographic areas, even within the tropics. For example, although TS 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

TS is confined to geographic regions but is observed in individuals of all races who live in or visit those regions.

Sex

The male-to-female ratio is equal.

Age

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

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• TS 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 TS exists; hence, these claims remain unsubstantiated. Patients may experience the following:
• • Diarrhea
  • Weight loss
  • Leg swelling
  • Fatigue
  • Fever

Physical

• 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 TS if the initial history, physical, and laboratory workups are suggestive of mucosal malabsorption.
• Although TS 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

• Environmental
• Residence or travel in an endemic tropical area

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

General fat malabsorption

Bacterial overgrowth
Ileal diseases
Pancreatic disorders

Mucosal diseases leading to malabsorption

AIDS enteropathy
Celiac sprue
Cryptosporidia
Giardiasis
Infectious causes
Nonspecific enteropathy
Norwalk virus
Radiation enteropathy
Intestinal lymphoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• 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

• 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.

Procedures

• 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

See Pathophysiology.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Patients with TS 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, TS 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 TS 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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Nutrient replacement to correct deficiencies in patients with TS 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.

Drug Category: Vitamins

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 TS commonly have deficiencies of folate and, sometimes, vitamin B-12.

Drug Name	Cyanocobalamin (Vitamin B-12, Crystamine, Cyomin)
Description	Water-soluble vitamin essential for normal erythropoiesis. Required for healthy neuronal functions and normal functions of rapidly growing cells.
Adult Dose	1000 mcg PO/IM; lower doses can be used; 30 mcg/d IM/SC for 5-10 d then 100-200 mcg/mo
Pediatric Dose	100 mcg IM/SC for 10-15 d then 60-100 mcg/mo IM/SC
Contraindications	Documented hypersensitivity to medicated or formula preparation product (benzyl alcohol) in neonates
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Diarrhea and itching may occur

Drug Category: Antibiotics

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

Drug Category: Minerals

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

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with TS 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 TS should undergo workup and evaluation as previously described (see Workup).

Further Outpatient Care

• 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.

In/Out Patient Meds

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

Deterrence/Prevention

• No direct evidence indicates that antibiotic prophylaxis can prevent TS.

Complications

• Anemia
• Malnutrition
• Vitamin deficiency

Prognosis

• Prognosis of this condition is generally good.

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 excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article Traveler's Diarrhea.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• As with any medical illness, physicians should make sure that the patient responds to the appropriate therapy after the diagnosis is made. If no response occurs, reevaluate the patients to make sure other mucosal causes of malabsorption or infectious causes (eg, protozoan illnesses) are not missed.
• TS may recur in patients living in endemic areas; therefore, retreatment may be necessary.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Cook GC. Aetiology and pathogenesis of postinfective tropical malabsorption (tropical sprue). Lancet. Mar 31 1984;1(8379):721-3. [Medline].
• Farthing MJ. Tropical malabsorption and tropical diarrhea. In: Feldman M, ed. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa: WB Saunders Co; 1998:1574-1584.
• Floch MH, Ozick L. Tropical sprue. In: Hurst JW, ed. Medicine for the Practicing Physician. 3rd ed. Boston, Mass: Butterworth;1992:1547-1549.
• French AB. Tropical sprue--specific disease or extreme of a spectrum?. Ann Intern Med. Jun 1968;68(6):1362-5. [Medline].
• Gilman AG, ed. The Pharmacological Basis of Therapeutics. 8th ed. New York, NY:. Pergamon Press Inc;1990.
• Greeberger NJ, Isselbacher KJ. Disorders of absorption. In: Fauci AS, ed. Harrison's Principle of Internal Medicine. 14th ed. New York, NY: McGraw-Hill;1998:1626.
• Klipstein FA, Baker SJ. Regarding the definition of tropical sprue. Gastroenterology. May 1970;58(5):717-21. [Medline].
• Klipstein FA. Tropical sprue--an iceberg disease?. Ann Intern Med. Mar 1967;66(3):622-3. [Medline].
• Klipstein FA. Tropical sprue in travelers and expatriates living abroad. Gastroenterology. Mar 1981;80(3):590-600. [Medline].
• Nath SK. Tropical sprue. Curr Gastroenterol Rep. Oct 2005;7(5):343-9. [Medline].
• Thielman NM, Guerrant RL. Persistent diarrhea in the returned traveler. Infect Dis Clin North Am. Jun 1998;12(2):489-501. [Medline].
• Toskes P. Malabsorption. In: Bennet JC, Plum F, eds. Cecil Textbook of Medicine. Philadelphia, Pa:. WB Saunders Co;1996:705-706.

Article Last Updated: Mar 13, 2006