Tropical Sprue

Etiology

The exact causative agent of tropical sprue remains unknown and is likely multifactorial in origin.[5] The prevailing hypothesis suggests that an acute intestinal infection initiates mucosal injury in the small bowel, leading to enterocyte damage. This injury impairs small intestinal motility, predisposing to small intestinal bacterial overgrowth.[6][7]

Proposed pathogenic mechanisms include intestinal injury from a toxic agent, nutritional deficiencies, or infectious processes. These factors may act independently or synergistically to produce mucosal damage and subsequent malabsorption.

• Toxins: Early hypotheses implicated rancid fats as a potential cause; however, evidence remains insufficient to support this theory.[8]
• Deficiency: Vitamin or mineral deficiencies have also been proposed as primary etiologic factors. Current evidence indicates these deficiencies are secondary to the disease rather than causative.[9]
• Infection: Bacterial infection is the most widely supported hypothesis. The prolonged latency period between exposure and symptom onset argues against toxins or nutritional deficiency as primary causes.[10] Symptomatic improvement with antibacterial therapy further supports an infectious etiology. While stool cultures from affected individuals have not demonstrated higher bacterial counts than controls, and mucosal biopsies have failed to show bacterial growth, proximal small bowel overgrowth of bacterial coliforms, including Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, has been documented.[11][12]

Epidemiology

The geographical distribution of tropical sprue remains incompletely understood. This condtion is observed in tropical regions, predominantly between latitudes 30° N and 30° S, although not all countries within this zone are affected.[12] In the Western Hemisphere, it is prevalent in Puerto Rico, Haiti, and Cuba, but absent in the Bahamas or Jamaica. In South Asia, this cindition is most frequently diagnosed in India, where it ranks second to celiac disease as a cause of malabsorption, and it is also prevalent in Pakistan.[13][14] The condition is rare in Africa, China, and the Middle East, with only isolated cases reported in the United States, however. 

Tropical sprue primarily affects both indigenous populations and travelers residing in endemic areas for more than 1 month and is uncommon in visitors staying less than 2 weeks. Incidence in India and Pakistan appears to be declining, likely due to improved hygiene and widespread antibiotic use.[15] Prevalence is similar in males and females, and while most cases occur in adults, pediatric cases have been reported.

Histopathology

In the early stages, small intestinal biopsy specimens may demonstrate normal mucosa. With disease progression, there is a gradual reduction in villous height, culminating in villous atrophy.[16] Other histologic features include increased crypt depth, nuclear immaturity, enlarged epithelial cells, intraepithelial lymphocytic infiltration, expansion of lamina propria inflammatory cells, and lipid deposition beneath the basement membrane.[17]

History and Physical

Tropical sprue presents with a wide range of clinical manifestations. Symptoms may develop shortly after travel to endemic regions or be delayed for years. The initial event is often an episode of gastroenteritis resembling traveler's diarrhea, after which bowel function fails to normalize. Patients typically experience persistent watery, foul-smelling diarrhea accompanied by bloating, crampy abdominal pain, borborygmi, and, in some cases, steatorrhea.[18] 

Anorexia and weight loss are common, whereas fever is uncommon. Malabsorption of vitamin B12 and folate may lead to anemia, manifesting as fatigue, pallor, and exertional dyspnea. Signs of malnutrition may include cold intolerance, irritability, impaired concentration, poor wound healing, and recurrent infections.[19] Physical examination findings can include glossitis, cheilitis, stomatitis, pedal edema, or abdominal distention. Casal necklace, characterized by a hyperpigmented rash around the neck classically associated with pellagra (niacin deficiency), has also been reported in association with tropical sprue.[20]

Evaluation

Multiple infections and inflammatory conditions can present with prolonged diarrhea and mimic tropical sprue. The diagnosis is established only after exclusion of these alternative causes.[21] The diagnostic workup includes radiographic and endoscopic evaluation, as well as blood and stool studies. Breath and urine testing may also be considered in selected cases. A complete blood count may reveal megaloblastic anemia associated with low vitamin B12 and folate levels; iron or vitamin D deficiencies may also be present. Elevated methylmalonic acid levels often accompany vitamin B12 deficiency, while both vitamin B12 and folate deficiencies are associated with high homocysteine levels, which may be found due to vitamin B12 or folate deficiency. A comprehensive metabolic panel may show electrolyte disturbances involving potassium, chloride, and sodium.

Infectious stool studies should be performed to exclude Giardia, Entamoeba, Strongyloides, and Cryptosporidium. Serological testing is recommended to rule out celiac disease.[22] Studies should be performed to assess the degree of malabsorption, most commonly by measuring fecal fat content and urinary D-xylose levels. A fecal fat content of 6 g or greater in 24 hrs while consuming 100 g of fat per day for 3 to 6 days before and during stool collection is considered abnormal and indicates fat malabsorption. The D-xylose test involves oral ingestion of 25 g of D-xylose; the result is positive if the 1-hour serum level is less than 20 mg/dL or the 5-hour urine excretion is less than 4 g.[3] 

Barium studies may reveal increased caliber and thickened mucosal folds of the small bowel.[23] Endoscopic evaluation often demonstrates duodenal and jejunal changes, involving villous atrophy, flattened or absent duodenal folds, and scalloped mucosal folds, and the presence of mucosal fissures.[24] The combination of steatorrhea, malabsorption of D-xylose and fat absorption, and characteristic biopsy findings of villous atrophy, crypt elongation, and an inflammatory cell infiltrate are adequate to confirm the diagnosis of tropical sprue in patients who have resided in or visited an endemic area for at least 1 month.[15][25][26] A favorable response to treatment further reinforces the diagnosis.

Treatment / Management

The management of tropical sprue requires a multimodal approach, emphasizing correction of malnutrition through mineral and vitamin supplementation and eradication of the underlying etiology with antibiotic therapy. Rarely, patients may present emergently with dehydration and weight loss; such cases require urgent evaluation and initiation of fluid and electrolyte replacement.[27] Hospitalization is indicated for complicated cases, including:

• Severe dehydration
• Significant electrolyte imbalance
• Symptomatic anemia

Treatment involves antibiotics, correction of electrolyte and micronutrient deficiencies, rehydration, parenteral vitamin B12 supplementation, and blood transfusions when indicated. Standard oral therapy consists of:

• Tetracycline 250 mg 4 times daily
• Trimethoprim-sulfamethoxazole (TMP-SMX) double strength 2 times daily
• A quinolone antibiotic
• Plus, iron and folic acid 5 mg daily

The usual duration is 3 to 6 months.[28][29] Therapy may be extended up to a year in endemic regions or patients with a relapsing disease.[30] Patients should be monitored for several months after completion of therapy to assess clinical improvement, weight gain, and normalization of hematologic and biochemical parameters.(B3)

Differential Diagnosis

The differential diagnosis of tropical sprue is extensive. Depending on the clinical presentation, 1 or more of the following conditions should be ruled out before establishing the diagnosis.

Infectious Conditions

• Entamoeba histolytica (amebiasis
• Giardia lamblia (giardiasis)
• Cystoisospora belli (cystoisosporiasis)
• Strongyloides stercoralis
• Cryptosporidium parvum (cryptosporidiosis)
• Cyclospora cayetanensis

Noninfectious Conditions

• Celiac disease
• Tropical enteropathies (environmental enteric dysfunction): Subclinical malabsorption of fats, carbohydrates, and vitamin B12, associated with typical radiographic and endoscopic findings characteristic of tropical sprue in lower socioeconomic populations in tropical areas. This condition may be the result of low-volume small intestinal bacterial overgrowth from ingestion of contaminated food and water.[5][22]
• Lactose intolerance
• Short bowel syndrome and blind loop syndrome
• Bile salt deficiency
• Small intestinal bacterial overgrowth
• Pancreatic insufficiency
• Tropical pancreatitis: A form of idiopathic chronic pancreatitis that is primarily seen in individuals from India and Africa, characterized by clinical symptoms similar to those of tropical sprue.
• Intestinal lymphoma
• AIDS enteropathy and related opportunistic infections
• Scleroderma involving the small intestine [31]

Prognosis

The prognosis of tropical sprue is generally favorable. Travelers who acquire the disease in endemic regions typically respond well to treatment, with minimal risk of recurrence. In contrast, recurrence rates among residents of endemic areas have been reported at approximately 20%, with some experiencing repeated relapses over time. More recent studies, however, suggest a trend toward improved outcomes, likely reflecting advances in hygiene and treatment practices.[30]

Complications

The morbidity and mortality associated with tropical sprue are generally low. The acute diarrheal phase is the most concerning, as severe electrolyte abnormalities and dehydration can be life-threatening and lead to adverse outcomes. Complications include progressive anemia, vitamin deficiencies, and malnutrition, leading to tissue damage and organ dysfunction. In prolonged disease, severe malnutrition can be fatal, particularly in patients with underlying comorbidities.[32]