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Synonyms: postinfective tropical malabsorption, idiopathic tropical malabsorption syndrome
Tropical sprue is a malabsorptive disease of the small bowel, characterised by inflammation and villous flattening in the small intestine. The symptoms and pathological appearance are similar to those of coeliac disease, but this is not an autoimmune condition and is considered most likely to be an infective one. The causative agent is, however, unclear, although it is probably bacterial. Tropical sprue is seen in residents of, and visitors to, tropical areas and it tends to begin with an acute episode of diarrhoea, fever and malaise before settling into a more chronic presentation of steatorrhea, malabsorption, nutritional deficiency, anorexia, malaise and weight loss. Folate deficiency is a significant part of the clinical picture.
Tropical sprue was epidemic during World War II and caused one sixth of all Allied casualties in India and Southeast Asia.
It is distinct from tropical enteropathy, an asymptomatic condition, defined by mild histological changes in the intestinal mucosa, which co-exists in endemic areas and is probably an adaptation to environmental factors.
- Tropical sprue usually occurs in residents of tropical or subtropical climates (less commonly, visitors), most often in developing countries.
- The condition may not present until after they have left the area. The lag can be up to 10 years.
- The incidence varies with geography.
- It occurs mostly in Southeast Asia and the Caribbean but not in Jamaica.
- It remains the most common cause of malabsorption in India.
- There is no predilection for race or gender.
- It tends to affect adults but can also occur in children.
- The aetiology is presumed to be infective but the exact cause remains elusive.
- The exact nature of the infection, whether initiated or perpetuated by enterotoxic coliform bacteria, viruses or a combination of pathogens, is not clear.
- Most commonly the condition only affects the upper small intestine although, more rarely, the stomach or colon can be involved.
Tropical sprue ranges in severity from subclinical structural or functional deficiencies of the gastrointestinal mucosa to a full picture of malabsorption with diarrhoea, malnutrition and loss of weight. This variable clinical picture can be incomplete and typically consists of chronic diarrhoea, weight loss and vitamin deficiencies.However it may include:
- Diarrhoea (acute or chronic).
- Weight loss.
- Malabsorption - deficiency of the following may occur:
- Iron, folate and vitamin B12 - are the most common, and there may be signs such as, pallor or glossitis.
- Vitamin A - with hyperkeratosis and skin scaliness.
- Vitamin D and calcium - may cause abdominal pain, bone pain, weakness, tingling.
- Vitamin K - risk of prolonged INR and haemorrhage.
- Abdominal pain - may be mild and does not usually dominate the clinical picture.
- Ankle oedema (hypoalbuminaemia).
- FBC - macrocytic anaemia with low folate and vitamin B12 levels in 60%.
- Serum potassium, iron and albumin - all may be low due to malabsorption and diarrhoea.
- Volume depletion is common - urea may be raised.
- Vitamin D.
- Calcium and phosphate may be abnormal, especially with low albumin.
- Malabsorption of D-xylose - a dose of 25 g xylose is given by mouth and normal results are that urine contains at least 20 mg per 100 ml at one hour and a total of 4g excreted in five hours. (Normal renal function is needed.) Lower results suggest malabsorption.
- Faecal fat measures - patients are fed a diet with high fat over 72 hours (80 to 100 g per day). A faecal fat exceeding 6 g a day is abnormal but steatorrhoea usually requires at least 15 g a day.
- Check stool - for cysts, ova and parasites.
- Consider bone densitometry - in appropriate patients.
- Jejunal biopsy - this shows incomplete villous atrophy (as opposed to coeliac disease where there is complete villous atrophy).
- Secondary malabsorption due to protozoal (eg, giardial), helminthic, bacterial, or viral infections.
- Coeliac disease.
- Crohn's disease.
- Tuberculosis of the gut can occur without pulmonary manifestations.
- Disease of the pancreas, causing pancreatic insufficiency.
- AIDS enteropathy.
- If vitamin B12 levels are very low, B12 replacement must start prior to folate replacement, as otherwise the demands of the haemopoietic system may precipitate subacute combined degeneration of the cord.
- Potassium supplements may also be needed as rapid utilisation occurs when haemaopotiesis starts. Failure to supplement may account for the occasional sudden death seen at the start of treatment for severe B12 deficiency.
- In children, delay in skeletal maturity, rickets, growth failure.
- Fluid volume replacement (electrolytes and water).
- Antibiotics - tetracycline is most often used and prolonged periods of treatment are necessary - eg, 6-12 months.
- Patients in southern India respond poorly to antibiotics.
- Tetracycline is not used in children whose permanent teeth have not yet come through, and another broad-spectrum antibiotic is substituted.
- In the USA, co-trimoxaxole is recommended although this drug is less commonly used in the UK.
- Nutritional supplements - for example:
- Folic acid - may need to be given parenterally at first if absorption is poor (but if very B12 deficient this must be replenished FIRST).
- Vitamin B12 injections - given daily for 5 to 10 days and then once a month. Absorption of vitamin B12 recovers early and so deficiency may be due to bacterial action rather than malabsorption.
- Oral iron may also be required, but iron and tetracycline should not be taken close to each other, as the tetracycline chelates the iron and neither is absorbed.
Treatment is monitored by
- Symptom improvement - eg, disappearance of anorexia with adequate B12 and folate replacement.
- Weight gain.
- Improvement of FBC and biochemical parameters.
- Untreated disease runs a chronic, relapsing course.
- Treatment is associated with a good prognosis.
- The diagnosis should be considered in any patient with diarrhoea and signs and/or symptoms of malabsorption who has spent more than two weeks in a tropical region where the disease is endemic.
- Improvement after folate replacement is prompt and dramatic. Failure to do so should elicit doubt about the diagnosis. Remember to replace vitamin B12 first if levels are very low.
- No causative microbe has been found, but the condition is likely to result from bacterial infection.
- In addition to folic acid supplementation, long-term treatment with antibiotics is currently recommended.
- Deficiencies of folic acid and vitamin B12 and resultant megaloblastic anaemia are the defining characteristics of the disease.
There is no established way to prevent the disease whilst visiting areas of risk. It seems sensible to observe safe practices regarding drinking water, peeling fruit and avoiding raw unpeeled vegetables, and this may minimise exposure to the causative agent.
In 1747 a Yorkshireman, Dr William Hillary, moved to Barbados to practise medicine. In 1759 he published one of the earliest books on tropical diarrhoeal disease, and he coined the term 'sprue'. in the book he describes chronic diarrhoea, malabsorption and weight loss occurring more frequently in Barbadians than in settlers. This was probably the first recorded account of tropical sprue.
Further reading and references
Ramakrishna BS, Venkataraman S, Mukhopadhya A; Tropical malabsorption. Postgrad Med J. 2006 Dec82(974):779-87.
Dutta AK, Balekuduru A, Chacko A; Spectrum of malabsorption in India--tropical sprue is still the leader. J Assoc Physicians India. 2011 Jul59:420-2.
Thielman NM, Guerrant RL; Persistent diarrhea in the returned traveler. Infect Dis Clin North Am. 1998 Jun12(2):489-501.
Bhatnagar S, Gupta SD, Mathur M, et al; Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children. J Pediatr Gastroenterol Nutr. 2005 Aug41(2):204-9.
Baqai MT; Duodenal tuberculosis: delays and difficulties in diagnosis. J R Coll Physicians Edinb 2005 35:330-331
Westergaard H; Tropical Sprue. Curr Treat Options Gastroenterol. 2004 Feb7(1):7-11.
Tomkins AM, Smith T, Wright SG; Assessment of early and delayed responses in vitamin B12 absorption during antibiotic therapy in tropical malabsorption. Clin Sci Mol Med Suppl. 1978 Dec55(6):533-9.
Bartholomew C; William Hillary and Sprue in the Caribbean, 230 Years Later, Gut Festschrift 1989, 17-21