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

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

Classification of pain in the abdomen based on etiology Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Abdominal causes Inflammatory causes Pancreato-biliary disorders Acute pancreatitis Epigastric + − + ± − − + − ± − − N Increased amylase / lipase Ultrasound shows evidence of inflammation CT scan shows severity of pancreatitis Pain radiation to back 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 ↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9  MDCT with  PET/CT MRI Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau's syndrome) Pancreatic panniculitis Gastric causes Dumping syndrome Lower and then diffuse − − + − − + + − + − − Hyperactive Glucose challenge test Hydrogen breath test Upper GI series Gastric emptying study Postgastrectomy Intestinal causes Acute appendicitis Starts in epigastrium, migrates to RLQ + Positive in pyogenic appendicitis + − − ± − − Positive in perforated appendicitis + + Hypoactive Leukocytosis Ct scan Ultrasound Positive Rovsing sign Positive Obturator sign Positive Iliopsoas sign Acute diverticulitis LLQ + ± + − + ± − + Positive in perforated diverticulitis + + Hypoactive Leukocytosis CT scan Ultrasound History of constipation Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease String sign on abdominal x-ray in Crohn's disease Extra intestinal findings: Uveitis Arthritis Irritable bowel syndrome Diffuse − − − − ± ± + − − − − N Normal Normal Symptomatic treatment High dietary fiber Osmotic laxatives Antispasmodic drugs Whipple's disease Diffuse ± − − ± − + + − ± − − N Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Tropical sprue Diffuse + − − − − + + − − − − N Fat soluble vitamin deficiency Hypoalbuminemia Fecal stool test Barium studies: Dilation and edema of mucosal folds Steatorrhea- 10-40 g/day (Normal=5 g/day) Celiac disease Diffuse − − − − − + + − − − − Hyperactive IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Small bowel biopsy US: Bull’s eye or target pattern Pseudokidney sign Gluten allergy Infective colitis Diffuse + − ± − − + − + Positive in fulminant colitis ± ± Hyperactive Stool culture and studies Shiga toxin in bloody diarrhea PCR CT scan Bowel wall thickening Edema Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments 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 Hepatic causes 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 CBC Blood cultures Abnormal liver function tests US CT Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Cirrhosis RUQ − − − + − − + + + − − N Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia US Nodular, shrunken liver Ascites Stigmata of liver disease Cruveilhier- Baumgarten murmur Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Hollow Viscous Obstruction Small bowel obstruction Diffuse + − + − + − + − + + ± Hyperactive then absent Leukocytosis with left shift indicates complications Abdominal X ray Dilated loops of bowel with air fluid levels Gasless abdomen "Target sign"– , indicative of intussusception Venous cut-off sign" – suggests thrombosis Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Vascular Disorders Ischemic causes Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock Hemorrhagic causes Ruptured abdominal aortic aneurysm Diffuse ± − + − − − + + + − − N Fibrinogen D-dimer Focused Assessment with Sonography in Trauma (FAST)  Unstable hemodynamics Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments