Tropical sprue differential diagnosis

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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]

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:

• Infectious causes
• Celiac disease
• Pancreatic insufficiency
• Osmotic diarrhea
• Secretory diarrhea

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 • Sigmoidoscopy or colonoscopy with biopsy • CT abdomen • UGI scopy and small bowel biopsy

1. Exclude structural disease by any/combination of the following tests • Small bowel radiographs • CT abdomen • Small bowel biopsy and aspirate for quantitative culture

• 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 • Sigmoidoscopy or colonoscopy with biopsy • CT abdomen • Biopsy of the proximal small bowel mucosa

2. Exclude infection by any/combination of the following tests: • Stool culture: Standard Aeromonas, Plesiomonas, Tuberculosis etc • Stool for ova and parasites • Clostridium toxin assay • Other specific test (Serology, ELISA, immunofluorescence to rule out virus and parasites)

2. Exclude exocrine pancreatic insufficieny by any/combination of the following tests: • Secretin test • Stool chymotrypsin activity • Bentiromide test • Others (D-xylose absorption tests / Schilling 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

Tropical sprue must be differentiated from other diseases that may cause chronic diarrhea, weight loss, and abdominal pain especially in immunocompromised patients.

Disease	Prominent clinical findings	Laboratory or radiological findings
Chronic giardiasis	Chronic giardiasis may develop after acute episode of giardiasis or without any acute events. Loose foul smelling stools Flatulence Fatigue Weight loss Steatorrhea Some patients develop acquired lactose intolerance (manifested by exacerbation of symptoms following ingestion of dairy products)	Microscopic identification of the organism in the stool Hypoalbuminaemia Vitamin B12 and folate deficiencies (as the organism inhabits the duodenum)
Cryptosporidiosis	Incubation period is 7-10 days. In immunocompetent patients: Disease might be asymptomatic or cause gastroenteritis (but without any biliary involvement) Gastroenteritis usually resolves spontaneously within 14 days. In immunocompromised patients: Disease is usually more severe and prolonged (especially in severly immunocomprmised patients with CD4 count < 100 cells/microL). Cryptosporidiosis may involve the biliary tract and the liver. Weight loss Abdominal RUQ tenderness might be present if biliary or hepatic involvement is present.	Microscopic identification of the organism in the stool: The oocysts appear red on staining with modified acid fast staining PCR: Most specific and sensitive diagnostic tool. PCR is expensive and used in limited cases.
Cystoisosporiasis (isosporiasis)	Cystoisosporiasis is usually seen in immunocompromised patients. Incubation period can last up to 2 weeks Watery diarrhea that is profuse and foul smelling Constitutional symptoms (headache, low grade fever, myalgia and malaise)	Isospora ova or parasites can be visualized on stool microscopic examination. Upper GI endoscopy may used for excluding other esophageal or gastric disease and obtaining specimens for histopathology.
Tropical sprue	History of travel to a tropical region (for a period more than a month) Chronic diarrhea Steatorrhea Examination may show signs of vitamin deficiencies (eg glossitis)	Megaloblastic anemia that might progress into pancytopenia Hypoalbuminaemia Vitamin D defeciency and hypocalcemia