Tropical sprue
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Synonyms and keywords: Postinfective tropical malabsorption, Sprue
Overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
Tropical sprue is a chronic diarrheal disorder of unclear etiology affecting the people in endemic and tropical regions.
Historical Perspective
The description of tropical sprue like disease was reported for the first time in Belgium. The name tropical sprue was coined by Sir Patrick Manson.
Classification
Tropical sprue is classified based on the duration of symptoms into acute phase and a chronic phase.
Pathophysiology
The exact pathophysiology of tropical sprue is unclear but is thought to be related to intestinal inflammation following an episode of diarrhea. The inflammation damages the intestinal villi and also result in lymphocytosis in the intestinal wall. Deficiency of lactase enzyme in results in malabsorption of carbohydrates and the dysfunctional enterocytes cause steatorrhea.
Causes
The exact etiological agent causing tropical sprue is unknown, but different bacteria types are identified in patients with tropical sprue.
Differentiating Tropical Sprue from other Diseases
Tropical sprue is a diagnosis of exclusion therefore it must be be differentiated from other diseases causing malabsorption such as celiac disease.
Epidemiology and Demographics
Tropical sprue is a rare diagnosis nowadays, and the highest prevalence is seen in the tropical countries.
Risk Factors
The risk factors for the development of tropical sprue include an episode of infectious diarrhea and visit to endemic areas.
Screening
Tropical sprue is a rare disease and a diagnosis of exclusion therefore no screening is recommended.
Natural History, Complications and Prognosis
Tropical sprue has an acute and a chronic phase and usually follows an episode of infectious diarrhea. The patients present with chronic non bloody diarrhea with malabsorption. The chronic phase can result in malabsorption and the patients will develop symptoms of vitamin B12 and vitamin A deficiency. The prognosis is excellent with treatment.
History and Symptoms
Patients with tropical sprue present with diarrhea, bloating, flatulence, fever and myalgias in the acute phase. Patients in the chronic phase present with features of malabsorption.
Physical Examination
The physical examination findings in acute phase can be significant for dehydration. In the chronic phase, features of sub acute combined degeneration of spinal cord and visual field defects are present.
Laboratory Findings
Tropical sprue is a diagnosis of exclusion and there are no specific laboratory findings. Blood smear will show megaloblastic changes in chronic phase of tropical sprue. All the etiologies of malabsorption must be ruled out to consider the diagnosis of tropical sprue.
Electrocardiogram
There are no ECG findings associated with tropical sprue.
X-Ray
X-Ray is not useful for the diagnosis of tropical sprue.
CT
CT has no role in the diagnosis of tropical sprue, however it is useful to rule out conditions such as inflammatory bowel disease and chronic pancreatitis.
MRI
MRI is not required for the diagnosis of tropical sprue.
Other Imaging Findings
Imaging studies are not required for the diagnosis of tropical sprue.
Other Diagnostic Studies
Upper GI endoscopy should be done to obtain a duodenal biopsy and the histological features suggestive of tropical sprue include intestinal villous blunting and intestinal lymphocytosis.
Medical Therapy
Folic acid and antimicrobial therapy are the mainstay of treatment for tropical sprue. Supportive therapy includes adequate hydration and replacement of nutrients such as iron and vitamin B12. Oral tetracycline is contraindicated among pregnant and lactating women and among children < 8 years of age. The main aims of treatment include: control of diarrhea, correction of existing vitamin deficiencies and cure of the disease.
Surgery
Surgery is not required for patients with tropical sprue. Antibiotic therapy alone is the modality of treatment.
Primary Prevention
The primary preventive measures include drinking clean water and maintaining good hygiene.
Secondary Prevention
There are no secondary preventive measures for tropical sprue.
References
Historical Perspective
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2] Akshun Kalia M.B.B.S.[3]
Overview
The description of tropical sprue like disease was reported for the first time in Belgium. The name tropical sprue was coined by Sir Patrick Manson.
Historical Perspective
- The word “sprue” is derived from a Dutch word “sprouw”. The term was used to describe a condition causing chronic diarrhea and aphthous ulcers in Belgium.
- In 1759, William Hillary, an English physician was the first to observe cases of chronic diarrhea in patients living in tropical areas.
- In 1880, the term tropical sprue was coined by Scottish physician, Sir Patrick Manson.
- In 1960’s, tropical sprue was thought to be the major cause of malabsorption in both adults and children.[1]
- In 1960’s, there was an epidemic of tropical sprue affecting 35,000 people in India.[2]
References
- ↑ BAKER SJ (1957). “Idiopathic tropical steatorrhea; a report of sixty cases”. Indian J Med Sci. 11 (9): 687–703. PMID 13474782.
- ↑ Mathan VI, Baker SJ (1968). “Epidemic tropical sprue and other epidemics of diarrhea in South Indian villages”. Am J Clin Nutr. 21 (9): 1077–87. PMID 5675846.
Classification
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
Tropical sprue is classified based on the duration of symptoms into acute phase and a chronic phase.[1]
Classification
Tropical sprue can be classified based on the duration of symptoms into the following:[2]
- Acute phase:
- Tropical sprue in acute phase is seen in visitors to tropical regions present with insidious onset, acute diarrhea with abdominal pain, nausea, and flatulence.
- Systemic symptoms such as fever, myalgia, and weakness may be present.
- Chronic phase:
- Tropical sprue in chronic phase is usually seen in resident population in the endemic regions.
- They present with diarrhea and symptoms of vitamin B12 and folate deficiencies which include stomatitis, glossitis, and anemia. This may take 2 to 4 years to develop.
References
- ↑ Brown IS, Bettington A, Bettington M, Rosty C (2014). “Tropical sprue: revisiting an underrecognized disease”. Am J Surg Pathol. 38 (5): 666–72. doi:10.1097/PAS.0000000000000153. PMID 24441659.
- ↑ Greenson, Joel K (2015). “The biopsy pathology of non-coeliac enteropathy”. Histopathology. 66 (1): 29–36. doi:10.1111/his.12522. ISSN 0309-0167.
Pathophysiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
The exact pathophysiology of tropical sprue is unclear but is thought to be related to intestinal inflammation following an episode of diarrhea. The inflammation damages the intestinal villi and also result in lymphocytosis in the intestinal wall. Deficiency of lactase enzyme in results in malabsorption of carbohydrates and the dysfunctional enterocytes cause steatorrhea.
Pathophysiology
Pathogenesis
Tropical sprue leads to villous atrophy which primarily affects the proximal and the distal gastrointestinal tract including the terminal ileum causing vitamin B12 and folate deficiencies. The pathogenesis of tropical sprue is unclear and multiple theories have been proposed. The pathogenesis of tropical sprue includes:[1]
- Post infectious diarrhea theory is the most supported due to:
- The occurrence of the disease following an episode of acute gastroenteritis.
- Occurrence of the disease in epidemics in rural areas with poor sanitation.
- Susceptibility of visitors from developed countries to endemic regions in developing countries.
- The frequency of small bowel bacterial overgrowth in patients with tropical sprue.
- The small intestinal bacterial overgrowth affects the enterocyte brush border activity, duodenal morphology causing villous atrophy and lymphocytosis in the intestinal cells.
- Other factors that can result in tropical sprue include the following:[2]
- Impaired host immune response results in prolonged inflammation of the small bowel affecting the enterocyte function.
- Reduced gut defense mechanisms results in increased bacterial overgrowth which damages the enterocytes and crypt cells leading to intestinal villous atrophy and eventually chronic diarrhea.
- Bile acid deconjugation affects the enterohepatic circulation and causes steatorrhea.
- Vitamin B12 deficiency can occur if the ileum is involved and the megaloblastic change in the intestinal musocal epithelium results in the formation of dysfunctional epithelial cells.
- Slow mouth to cecum transit due to intestinal stasis promotes small intestinal bacterial over growth and patients with tropical sprue have higher levels of enteroglucagon, peptide YY, and neurotensin which decrease the motility of intestine all these can predispose to the development of tropical sprue.[3]
- Mucosal disaccharidase deficiency is also a potential cause as patients with tropical sprue have higher levels of urinary lactuose excretion suggesting a deficiency of lactase enzyme.
- The bacteria after an episode of diarrhea damages the enterocytes resulting in small bowel stasis, bacterial over-growth, reduced gut motility, malabsorption and loss of folate with further damage to the enterocyte. All these factors contribute to the vicious cycle of events resulting in tropical sprue.
- Treatment with tetracyclines eliminates the bacterial overgrowth and supplementation of folate helps in regeneration of the intestinal epithelium. The diagnosis of tropical sprue is confirmed only if the patient responds to treatment with tetracyclines and folate supplementation.
Genetics
People with Aw-19 HLA haplotype are at higher risk of developing tropical sprue.
Associated Conditons
There are no associated conditions with tropical sprue.
Microscopic Pathology
- Small bowel biopsy reveals similar changes as gluten sensitive enteropathy.
- The features demonstrated on a duodenal biopsy include:[4]
- Incomplete villous blunting
- Intra epithelial lymphocytosis
- Eosinophilic infilteration of the mucosa
References
- ↑ Ghoshal UC, Kumar S, Misra A, Choudhuri G (2013). “Pathogenesis of tropical sprue: a pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake”. Indian J Med Res. 137 (1): 63–72. PMC 3657900. PMID 23481053.
- ↑ Brown, Ian S.; Bettington, Andrew; Bettington, Mark; Rosty, Christophe (2014). “Tropical Sprue”. The American Journal of Surgical Pathology. 38 (5): 666–672. doi:10.1097/PAS.0000000000000153. ISSN 0147-5185.
- ↑ Ghoshal UC, Ghoshal U, Ayyagari A, Ranjan P, Krishnani N, Misra A; et al. (2003). “Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time”. J Gastroenterol Hepatol. 18 (5): 540–7. PMID 12702046.
- ↑ SWANSON VL, THOMASSEN RW (1965). “PATHOLOGY OF THE JEJUNAL MUCOSA IN TROPICAL SPRUE”. Am J Pathol. 46: 511–51. PMC 1920377. PMID 14278662.
Causes
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
The exact etiological agent responsible for causing tropical sprue is unknown, but different types of bacteria are identified in patients with tropical sprue.
Causes
Small bowel bacterial overgrowth is thought to be the primary cause for tropical sprue but the exact cause of tropical sprue is still unknown. Tropical sprue occurs in regions where enteric infections are common and the most common bacteria isolated in patients with tropical sprue include:[1][2][3]
References
- ↑ Gorbach SL, Mitra R, Jacobs B, Banwell JG, Chatterjee BD, Mazumder DN (1969). “Bacterial contamination of the upper small bowel in tropical sprue”. Lancet. 1 (7585): 74–7. PMID 4178002.
- ↑ Klipstein FA, Short HB, Engert RF, Jean L, Weaver GA (1976). “Contamination of the small intestine by enterotoxigenic coliform bacteria among the rural population of Haiti”. Gastroenterology. 70 (6): 1035–41. PMID 773737.
- ↑ Bhat P, Shantakumari S, Rajan D, Mathan VI, Kapadia CR, Swarnabai C; et al. (1972). “Bacterial flora of the gastrointestinal tract in southern Indian control subjects and patients with tropical sprue”. Gastroenterology. 62 (1): 11–21. PMID 4551005.
Differentiating Tropical sprue from other Diseases
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2] Akshun Kalia M.B.B.S.[3]
Overview
Tropical sprue should be differentiated from diseases causing chronic diarrhea and malabsorption such as celiac disease, osmotic diarrhea and secretory diarrhea.
Differentiating Tropical Sprue from other Diseases
Tropical sprue is a diagnosis of exclusion therefore it must be be differentiated from other diseases causing malabsorption such as: [1][2][3][4]
Approach to a Patient with Chronic Diarrhea
The following is an algorithm describing the approch to a patient with chronic diarrhea:
| Classify diarrhea by the results of the stool analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Stool osmotic gap >50 mOsm/kg | Stool osmotic gap <50 mOsm/kg | Fecal occult blood (+), WBC (+), lactoferrin (+), calprotectin(+) | Fecal fat (+) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osmotic diarrhea | Secretory diarrhea | Inflammatory diarrhea | Fatty diarrhea | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| • Check the pH of the stool | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Low pH • Evaluate for carbohydrate malabsorption | High pH • Evaluate for ingestion of magnesium or antacids • Evaluate for laxative abuse | 1. Exclude infection by any/combination of the following tests:
• Stool culture • Microscopic evaluation for ova and parasites • Stool antigen test for Giardia • Small bowel aspirate or breath H2 test to rule out bacterial overgrowth | 1. Exclude structural disease by any/combination of the following tests:
• Small bowel radiographs | 1. Exclude structural disease by any/combination of the following tests
• Small bowel radiographs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| • Take a careful dietary history • Order breath H2 test (lactose), OR • Order lactase measurement in a mucosal biopsy | • Order stool alkanization test • Order chromatographic and chemical tests | 2. Exclude structural disease by any/combination of the following tests:
• Small bowel radiographs | 2. Exclude infection by any/combination of the following tests:
• Stool culture: Standard Aeromonas, Plesiomonas, Tuberculosis etc | 2. Exclude exocrine pancreatic insufficieny by any/combination of the following tests:
• Secretin test | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3. Order selective testing:
• Cholestyramine test for bile acid diarrhea • Plasma peptides (Gastrin, calcitonin, vasoactive intestinal polypeptide or somatostatin) • Urine (5-hydroxyindole acetic acid, metanephrine or histamine) • Others (TSH, ACTH stimulation test, serum protein electrophoresis or serum immunoglobulins) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Confirmatory diagnosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Specific treatment per results and symptomatic treatment | Suspect Tropical sprue and initiate antibiotic therapy and folate supplementation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Differentiating Tropical Sprue from Other causes of Fat Malabsorption
Tropical sprue must also be differentiated from other causes of fat malabsorption such as Whipple’s disease, celiac disease, pancreatic disorders and other less common conditions.
Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram, US = Ultrasound
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Differentiating Tropical Sprue from Other causes of Fat Malabsorption in Immunocompromised Patients
Tropical sprue must be differentiated from other diseases that may cause chronic diarrhea, weight loss, and abdominal pain especially in immunocompromised patients. These conditions include chronic giardiasis, cryptosporidiosis, Cystoisosporiasis (isosporiasis)[5][6][7][8]
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References
- ↑ Dosanjh G, Pardi DS (2016). “Chronic unexplained diarrhea: a logical and cost-effective approach to assessment”. Curr Opin Gastroenterol. 32 (1): 55–60. doi:10.1097/MOG.0000000000000232. PMID 26628100.
- ↑ Langenberg MC, Wismans PJ, van Genderen PJ (2014). “Distinguishing tropical sprue from celiac disease in returning travellers with chronic diarrhoea: a diagnostic challenge?”. Travel Med Infect Dis. 12 (4): 401–5. doi:10.1016/j.tmaid.2014.05.001. PMID 24889052.
- ↑ Corinaldesi R, Stanghellini V, Barbara G, Tomassetti P, De Giorgio R (2012). “Clinical approach to diarrhea”. Intern Emerg Med. 7 Suppl 3: S255–62. doi:10.1007/s11739-012-0827-4. PMID 23073866.
- ↑ Juckett G, Trivedi R (2011). “Evaluation of chronic diarrhea”. Am Fam Physician. 84 (10): 1119–26. PMID 22085666.
- ↑ Current WL, Garcia LS (1991). “Cryptosporidiosis”. Clin. Microbiol. Rev. 4 (3): 325–58. PMC 358202. PMID 1889046.
- ↑ Thompson RC (2000). “Giardiasis as a re-emerging infectious disease and its zoonotic potential”. Int. J. Parasitol. 30 (12–13): 1259–67. PMID 11113253.
- ↑ Sánchez-Vega JT, Tay-Zavala J, Aguilar-Chiu A, Ruiz-Sánchez D, Malagón F, Rodríguez-Covarrubias JA, Ordóñez-Martínez J, Calderón-Romero L (2006). “Cryptosporidiosis and other intestinal protozoan infections in children less than one year of age in Mexico City”. Am. J. Trop. Med. Hyg. 75 (6): 1095–8. PMID 17172373.
- ↑ Klipstein FA, Schenk EA (1975). “Enterotoxigenic intestinal bacteria in tropical sprue. II. Effect of the bacteria and their enterotoxins on intestinal structure”. Gastroenterology. 68 (4 Pt 1): 642–55. PMID 1091526.
Epidemiology and Demographics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2] Akshun Kalia M.B.B.S.[3]
Overview
Tropical sprue is a rare diagnosis nowadays, and the highest prevalence is seen in the tropical countries.
Epidemiology and Demographics
Incidence
- The incidence of tropical sprue is unknown as it is a rare diagnosis due to improved hygiene practices and the use of antibiotics.[1]
- In United States, tropical sprue is extremely rare and is only seen in travellers to endemic areas.
Geography
- Tropical sprue affects the people tropical areas (30 degrees North or South of the equator), India, major part of South East Asia, Puerto Rica, parts of the Caribbean, northern South America, and West Africa have high prevalence of tropical sprue.[1]
Age
- Tropical sprue commonly affects adults. However, cases in children have also been reported.
Gender
- Tropical sprue affects men and women equally.
Race
- Tropical sprue affects all races of those who reside or visit endemic areas.[1][2]
References
Risk Factors
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
The risk factors for the development of tropical sprue include an episode of infectious diarrhea and visit to tropical areas.
Risk Factors
Risk factors associated with tropical sprue include: [1]
- Episode of infectious gastroenteritis[2]
- Reduced bowel motility
- Visit to endemic tropical area
References
- ↑ Brown IS, Bettington A, Bettington M, Rosty C (2014). “Tropical sprue: revisiting an underrecognized disease”. Am J Surg Pathol. 38 (5): 666–72. doi:10.1097/PAS.0000000000000153. PMID 24441659.
- ↑ McCarroll MG, Riddle MS, Gutierrez RL, Porter CK (2015). “Infectious Gastroenteritis as a Risk Factor for Tropical Sprue and Malabsorption: A Case-Control Study”. Dig Dis Sci. 60 (11): 3379–85. doi:10.1007/s10620-015-3768-8. PMID 26115751.
Screening
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
There is no standard recommendation screening for tropical sprue.
Screening
Tropical sprue is a rare disease and a diagnosis of exclusion therefore no screening is recommended.
References
Natural History, Complications and Prognosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
Tropical sprue has an acute and a chronic phase and usually follows an episode of infectious diarrhea. The patients present with chronic non bloody diarrhea with malabsorption. The chronic phase can result in malabsorption and the patients will develop symptoms of vitamin B12 and vitamin A deficiency. The prognosis is excellent with treatment.
Natural History, Complications and Prognosis
Natural History
Tropical sprue is a diagnosis of exclusion, patients present with chronic non-bloody diarrhea, abdominal bloating and flatulence following an episode of infectious diarrhea. Patients with chronic form of tropical sprue presents with features of vitamin B12 and vitamin A deficiencies. If left untreated it is associated with significant morbidity and mortality, therefore suspicion of tropical sprue must be high if histology of the duodenal biopsy demonstrates villous atrophy and if the patient is unresponsive to a gluten free diet.[1]
Complications
The complications of tropical sprue include:[2]
- Vitamin B12 deficiency causes sub acute combined degeneration of the spinal cord resulting in neurological symptoms.
- Vitamin A deficiency causes visual disturbances and night blindness.
- Hypokalemia can occur due to chronic diarrhea.
Prognosis
All the patients with tropical sprue have excellent prognosis with tetracycline treatment. Treatment is continued for a period of 6 months but the symptoms resolve within 2 to 3 weeks from initiation of therapy.[3]
References
- ↑ Walker MM (2003). “What is tropical sprue?”. J Gastroenterol Hepatol. 18 (8): 887–90. PMID 12859716.
- ↑ Brown IS, Bettington A, Bettington M, Rosty C (2014). “Tropical sprue: revisiting an underrecognized disease”. Am J Surg Pathol. 38 (5): 666–72. doi:10.1097/PAS.0000000000000153. PMID 24441659.
- ↑ Rickles FR, Klipstein FA, Tomasini J, Corcino JJ, Maldonado N (1972). “Long-term follow-up of antibiotic-treated tropical sprue”. Ann Intern Med. 76 (2): 203–10. PMID 5009590.
Diagnosis
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Treatment
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
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