Lawrence R. Schiller, M.D., F.A.C.P.
Baylor University Medical Center

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Frequent passage of loose stools for more than 4 wk
• Classified according to stool characteristics (i.e., watery, inflammatory, or fatty)
  • Blood and pus in stools are typical of inflammatory diarrhea, although a range of underlying inflammatory diseases (e.g., inflammatory bowel disease, infections, ischemia, radiation enteritis, and neoplasia) may also produce watery, secretory diarrhea without blood or pus
    
    

Differential Diagnosis

Secretory Diarrhea
• Bacterial toxins
• Congenital syndromes
• Ileal bile acid malabsorption
• Microscopic colitis and other inflammatory bowel disease
• Diverticulitis
• Medications and toxins
• Laxative abuse
• Surgical complications (e.g., following gastric bypass, vagotomy, pyroplasty, bowel resection, ileostomy, cholecystectomy)
• Diabetes mellitus and associated complications
• Opportunistic infections or lymphoma associated with HIV
• Neuroendocrine tumors
• Idiopathic secretory diarrhea


Osmotic diarrhea
• Carbohydrate malabsorption
• Magnesium ingestion

Inflammatory diarrhea
• Invasive/ulcerating infections
• Inflammatory bowel disease
• Diverticulitis
• Ischemia/radiation injury
• Neoplasia

Fatty diarrhea
• Malabsorption syndrome
  • Mucosal diseases
  • Short bowel syndrome
  • Small bowel bacterial overgrowth
  • Mesenteric ischemia
• Maldigestion
  • Pancreatic exocrine insufficiency
  • Bile acid deficiency

Clinical Pearls
• An important goal is to distinguish between diarrhea associated with irritable bowel syndrome (which is characterized by abdominal pain during defecation and altered bowel habits) and diarrhea associated with other functional or organic problems




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Best Tests

• Medical history
  • A thorough and accurate medical history is essential and should elicit the following information:
    • Onset, pattern, and duration of diarrhea
    • Stool characteristics (i.e., watery, bloody, fatty)
    • Long-term trends in body weight
    • Current appetite and food intake
    • Previous medical problems and surgeries
    • Previous evaluations and treatments
    • Clues pointing to other systemic illnesses
• Physical examination
  • In addition to revealing the severity of the patient's condition, signs and symptoms should yield additional etiologic clues
    • Characteristic skin changes indicative of mastocytosis, glucagonoma, Addison disease, amyloidosis, carcinoid syndrome, Degos disease, and celiac disease
    • Orthostatic hypotension and hepatosplenomegaly may be associated with amyloidosis
    • Hepatosplenomegaly, edema, right-sided heart murmur, and flushing may indicate carcinoid syndrome
    • Presence of arthritis may indicate inflammatory bowel disease, Whipple disease, or enteric infection
    • Absence of peripheral arterial pulses or presence of bruits may indicate mesenteric vascular disease
    • Defective sphincter or pelvic muscle floor function, as revealed by rectal examination, is associated with fecal incontinence
• Routine laboratory evaluation
  • Stool analysis (i.e., sodium and potassium concentrations, osmolality, pH, electrolyte concentrations) facilitates categorization and should be obtained through a random sample or timed collection

Recommended Evaluations Based on Stool Characteristics
Watery Secretory Diarrhea
• Because of its broad differential diagnosis, a thorough evaluation is warranted and may include the following tests:
  • Stool culture: Can exclude infection
  • Biopsy of the small colon or bowel: Used to determine implicating pathogens in immunocompromised patients
  • Radiographic and endoscopic testing: Should be conducted to identify structural disease
  • CT: Can detect small bowel and colonic disease
  • Colonoscopic or sigmoidoscopic evaluation of the colonic mucosa: Essential to evaluate gross changes and obtain biopsy samples indicative of microscopic colitis syndrome
  • Serum peptide or urinary secretagogue metabolite measures: Should be restricted to patients with symptoms consistent with tumor syndromes or in whom diagnosis is uncertain following initial testing
  • A trial of bile acid–binding resins: Can be used in patients with apparent idiopathic secretory diarrhea to determine if bile acid malabsorption plays a role in the patient's condition
Watery Osmotic Diarrhea
• Low electrolyte concentrations indicate that some other substance, usually ingested magnesium or malabsorbed carbohydrates, is taking up osmotic space and holding water in the lumen
  • Magnesium excretion of > 15 mmol daily or concentration > 45 mmol in a random stool sample is indicative of intentional or accidental magnesium-induced diarrhea
  • Stool pH < 6 coupled with a thorough dietary history may reveal carbohydrate malabsorption
• Other common causes of osmotic diarrhea include excessive fructose, poorly absorbed sugar alcohols (e.g., sorbitol, mannitol), and use of carbohydrate inhibitors (e.g., acarbose)
Chronic Inflammatory Diarrhea
• Endoscopic and radiographic evaluations should be conducted to determine the presence of structural problems:
  • Consider sigmoidoscopy or colonoscopy first since colitis is a common cause of inflammatory diarrhea; biopsies can be performed to categorize colitis
  • CT scans often reveal inflammatory changes in the small bowel and colon and identify complications (e.g., abscess)
• Rule out infections that produce chronic diarrhea by culture, biopsy, or serologic testing, particularly in patients with HIV who are prone to opportunistic infections
Chronic Fatty Diarrhea
• Because the common criteria to define steatorrhea (i.e., stool fat output > 7 g/24 hours or > 9% daily intake) are often invalid in patients with diarrhea, the threshold should be corrected for fat intake and estimated from diet diaries maintained during timed stool collection whenever possible
  • Substitute qualitative estimation of fat excretion by Sudan stain of fecal smears when timed collection or quantitative analysis is impossible
• Fecal fat concentration may provide a clue to the etiology of steatorrhea (e.g., low in mucosal disease, high in pancreatic exocrine insufficiency, lack of bile acids)
  • Concentrations > 9.5g/100 g are strong indicators of pancreatic or biliary steatorrhea
• If the cause of steatorrhea remains unclear, evaluation of the absorptive surface of the small intestine by endoscopic, histologic, and radiographic tests is recommended
  • If the absorptive surface is normal, consider luminal problems with fat solubilization or digestion
  
  

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Best Therapy

Nonspecific Drug Therapy

• Antidiarrheals, routine dosing (i.e., scheduled before mealtime or bedtime) is more effective than dosing “as needed” or after passing stools
  • Diphenoxylate with atropine
    • Dose: lowest effective single dose, 2.5 mg (1 tablet) t.i.d., p.o.; daily max, 20 mg (8 tablets)
    • Cost/30 days: $42 to $111
  • Difenoxin with atropine
    • Dose: lowest effective single dose, 1 mg (1 tablet) t.i.d., p.o.; daily max, 8 mg (8 tablets)
  • Loperamide (2 mg)
    • Dose: lowest effective single dose, 2 mg t.i.d.; daily max, 16 mg
    • Cost/30 days: $24 to $66
• Potent opiates, often underutilized in patients unresponsive to simple antidiarrheals
  • Deodorized tincture of opium (10 mg morphine/ml)
    • Dose: lowest effective single dose, 5 drops q.i.d.; daily max, 80 drops
  • Paregoric (0.4 mg morphine/ml)
    • Dose: lowest effective single dose, 5 ml q.i.d.; daily max, 40 ml
    • Cost/6–12 days: $86
  • Morphine sulfate (20 mg/ml)
    • Dose: lowest effective single dose, 2 drops q.i.d.; daily max, 40 drops
  • Codeine phosphate or sulfate
    • Dose: lowest effective single dose, 15 mg q.i.d.;daily max, 240 mg
• Stool modifiers/intraluminal agents may be of special help in patients with concomitant fecal incontinence
  • Psyllium
    • Dose: lowest effective single dose, 18 g/24 hr; daily max, 30 g/24 hr
    • Cost/22–37 days: $11
Therapy for Specific Syndromes
Osmotic Diarrhea
• Fasting or elimination of offending agent from diet will cause symptoms to abate unless other diarrhea-producing mechanisms are still active (e.g., short bowel syndrome, diseases of small bowel mucosa)
  



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Best References

Fine KD, et al: Gastroenterology 116:1464, 1999 [PMID 10348832]

Hasler WL: Dumping syndrome. Curr Treat Options Gastroenterol 5:139, 2002 [PMID 11879594]

Kalantzis N, et al: Hepatogastroenterology 52:414, 2005 [PMID 15816447]

Schiller LR: Med Clin North Am 84:1259, 2000 [PMID 11026928]

Schiller LR: Aliment Pharmacol Ther 9:87, 1995 [PMID 7605866]

The author has received grants for educational activities from and served as an advisor for Novartis Pharmaceuticals Corp., GlaxoSmithKline, Romark Laboratories, Salix Pharmaceuticals, Inc., Santarus, Inc., and Takeda Pharmaceuticals North America, Inc.; has received grants for clinical research from Novartis Pharmaceuticals Corp. and GlaxoSmithKline; and has served as an advisor to TAP Pharmaceutical Products, Inc.

March 2009


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