Tropical sprue (TS) is an acquired intestinal malabsorption syndrome of unknown etiology that affects residents and tourists of tropical regions including West Africa, Central America, South America, the Caribbean, Puerto Rico, South East Asia and the Indian subcontinent [1
]. It still accounts for almost 40% of malabsorption in adults and children in South Asia [2
]. TS has not been described in Jamaica or sub-Saharan Africa [6
]. The etiology remains elusive, but it has been suggested that persistent infection may be responsible and it is also referred to as ‘post-infective tropical malabsorption’ [7
]. Contamination of the small bowel by aerobic enteric bacteria is seen with TS patients, but no specific causal agent has ever been found [9
]. Several studies have also shown increased frequency of HLA antigens Aw19 and Aw31 in Puerto Rican patients [11
Histological findings in TS may be indistinguishable from those in celiac disease which is part of the differential diagnosis for TS. However, TS involves the entire length of the small bowel while celiac disease typically spares the terminal ileum. Villous blunting is noted, but the complete villus flattening that can be seen in celiac disease is rare in TS [13
]. Small intestine bacterial overgrowth histology may look identical to TS, however risk factors for dysmotility and stasis usually exist. Crypt hyperplasia and epithelial cell dysfunction in the proximal and distal small intestine contribute to multiple nutrient deficiencies. Reduced absorption of carbohydrates (xylose), fat, and fat-soluble vitamins is seen. Proximal small bowel involvement results in iron and folate deficiencies while terminal ileum involvement can cause vitamin B12 deficiency and bile acid malabsorption, which may further exacerbate diarrhea [5
Symptoms of TS include chronic nonbloody diarrhea, weight loss, bloating, and abdominal cramps. Physical exam may reveal pallor, angular stomatitis, glossitis, mouth ulcers, and peripheral edema due to protein deficiency. In severe cases, vitamin A deficiency can result in night blindness, and chronic low vitamin B12 levels may cause neurologic symptoms due to subacute combined degeneration of the spinal cord.
Management begins with restoring fluid and electrolytes and repleting vitamin deficiencies. Parenteral vitamin B12, oral folate and iron supplementation can result in improvement in symptoms and weight gain even before intestinal absorption. Folate supplementation (1-5 mg daily) can result not only in improvement of the macrocytic anemia, but also in improvement in villi structure [16
]. A quick and dramatic symptomatic response with folate therapy is observed so frequently in TS and so rarely in other forms of small bowel disease with megaloblastic anemia that it is considered to be diagnostic of the illness [18
]. Antibiotics are commonly used with the preferred agents being tetracycline (250 mg four times daily) and doxycycline (100 mg daily) for 3–6 months [5
]. Dietary restriction on long-chain fatty acids also helps to reduce diarrhea [5
]. Travellers returning to nontropical regions will generally recover completely after treatment, however relapse rates of 20–50% are seen in people permanently residing in endemic regions [5
A typical scenario that may be seen in the United States is that of a patient with chronic diarrhea who has lived or recently visited a tropical region. The acute illness likely started overseas and resolved within about a week, but then the patient continues to experience a milder form of persistent diarrhea with ongoing malaise and weight loss. No definite infectious source is identified and laboratory tests may reveal megaloblastic anemia due to folate and/or vitamin B12 deficiency. In addition, the levels of other vitamins like A and D may also be reduced. Upper endoscopy generally reveals normal mucosa, but small bowel biopsies will show an increase in intraepithelial lymphocytes and blunting of villi (total villous atrophy which can be seen in celiac disease is not a common in TS). If performed, a 100 g fat diet 72-hour fecal fat collection test will be abnormal in most patients.
Both of our patients presented to us with chronic nonbloody diarrhea and weight loss after having lived in parts of the world where TS is endemic. No specific infection was found in either, and although celiac disease was in the differential diagnosis, clinical, serologic, and histologic evidence did not support the diagnosis. The index of suspicion for TS should be high in such cases and a course of tetracycline and folic acid in both of our patients led to dramatic improvement relatively quickly, and remission has been maintained.