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] 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
 
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[5]
Cryptosporidiosis[6]
  • Disease might be asymptomatic or cause gastroenteritis (but without any biliary involvement)
  • Gastroenteritis usually resolves spontaneously within 14 days.
  • 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)[7]
  • 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[8]
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

Disease Clinical manifestations Diagnosis Comments
Symptoms Signs
Abdominal Pain Fever Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging
Tropical sprue Diffuse + + + N Barium studies:
  • Dilation and edema of mucosal folds
Whipple's disease Diffuse ± ± + + ± N Endoscopy is used to confirm diagnosis.

Images used to find complications

Extra intestinal findings:
Celiac disease Diffuse + + Hyperactive US:
  • Bull’s eye or target pattern
  • Pseudokidney sign
  • Gluten allergy
Acute pancreatitis Epigastric + + ± + ± N
  • Ultrasound shows evidence of inflammation
  • CT scan shows severity of pancreatitis
  • Pain radiation to back
Disease Abdominal Pain Fever Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments
Chronic pancreatitis Epigastric ± ± + + N
  • Increased amylase / lipase
  • Increased stool fat content
  • Pancreatic function test
CT scan
  • Calcification
  • Pseudocyst
  • Dilation of main pancreatic duct
  • Predisposes to pancreatic cancer
Pancreatic carcinoma Epigastric + + + + N

Skin manifestations may include:

Dumping syndrome Lower and then diffuse + + + + Hyperactive
  • Postgastrectomy
Acute diverticulitis LLQ + + + ± + Positive in perforated diverticulitis + + Hypoactive
  • CT scan
  • Ultrasound
Inflammatory bowel disease Diffuse ± ± + + + Normal or hyperactive

Extra intestinal findings:

Disease Abdominal Pain Fever Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments
Irritable bowel syndrome Diffuse ± ± - N Normal Normal Symptomatic treatment
Infective colitis Diffuse + ± + + Positive in fulminant colitis ± ± Hyperactive CT scan
  • Bowel wall thickening
  • Edema
Colon carcinoma Diffuse/ RLQ/LLQ ± ± + + ±
  • Normal or hyperactive if obstruction present
  • CBC
  • Carcinoembryonic antigen (CEA)
  • Colonoscopy
  • Flexible sigmoidoscopy
  • Barium enema
  • CT colonography 
  • PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction
Viral hepatitis RUQ + + + Positive in Hep A and E + Positive in fulminant hepatitis Positive in acute + N
  • Abnormal LFTs
  • Viral serology
  • US
  • Hep A and E have fecal-oral route of transmission
  • Hep B and C transmits via blood transfusion and sexual contact.
Liver abscess RUQ + + + ± + + + ± Normal or hypoactive
  • US
  • CT
Cirrhosis RUQ + + + + N US
  • Stigmata of liver disease
  • Cruveilhier- Baumgarten murmur

References

  1. 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.
  2. 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.
  3. 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.
  4. Juckett G, Trivedi R (2011). "Evaluation of chronic diarrhea". Am Fam Physician. 84 (10): 1119–26. PMID 22085666.
  5. Thompson RC (2000). "Giardiasis as a re-emerging infectious disease and its zoonotic potential". Int. J. Parasitol. 30 (12–13): 1259–67. PMID 11113253.
  6. 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.
  7. Current WL, Garcia LS (1991). "Cryptosporidiosis". Clin. Microbiol. Rev. 4 (3): 325–58. PMC 358202. PMID 1889046.
  8. 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.