Best Dx/Best Rx: Diarrheal Diseases

From: Subject: Best Dx/Best Rx: Diarrheal Diseases Date: Wed, 3 Jun 2009 21:09:17 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0122_01C9E48F.8E6BB750" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0122_01C9E48F.8E6BB750 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0403.htm Best Dx/Best Rx: Diarrheal Diseases

Diarrheal=20 Diseases
Acute=20 Diarrhea
Ch= ronic=20 Diarrhea

Acute = Diarrhea=20

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

Definition/Key Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References=20

Definition/Key=20 Clinical Features

Frequent passage of watery, loose stools = lasting less=20 than 4 wk=20
Loose or =93pourable=94 stools=20
More than two bowel movements daily=20
Increased stool weight (i.e., > 200 g/24 = hr)=20
Abdominal pain=20
Cramps=20
Bloating=20
Flatulence=20
Fever

=20 bac= k to=20 top

Differential = Diagnosis

Food allergy=20
Medication reaction=20
Inflammatory bowel disease =

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Best=20 Tests

Medical history=20
- Probe for acuity and severity of the = diarrheal=20 process=20
- Probe for use of medications, including=20 over-the-counter and herbal products, and evaluate current = diet=20
- Investigate recent family history, travel, = occupation,=20 sexual activity, illicit drug use, and water source =
Physical examination=20
- Assess stool volume status by looking for = orthostatic=20 changes in blood pressure and pulse=20
- Evaluate presence of fever and other signs = of=20 toxicity=20
- Examine abdomen for bowel sounds and = presence of=20 distention or tenderness=20
- Manifestations of volume depletion (i.e., = orthostasis,=20 thirst, decreased urine output, weakness) are suggestive of = voluminous=20 diarrhea

Clinical=20 Pearls=20

Laboratory evaluation (i.e., a complete blood = count)=20 should be reserved for patients presenting with toxicity, dehydration, = or=20 diarrhea persisting longer than expected given the probable = cause=20
- Serum electrolytes, blood urea nitrogen, and = serum=20 creatinine measure volume and electrolyte depletion=20
- Stool cultures may be of value in patients = with blood=20 in the stool, dehydrating or prolonged diarrhea, or dysentery (or = those=20 presenting during a disease outbreak)
Sigmoidoscopy or colonoscopy may be considered = for=20 patients who are toxic or who present with blood in the stool or = persistent=20 diarrhea=20
Abdominal x-rays or CT should be obtained in = toxic=20 patients to confirm colitis and to look for evidence of ileus or=20 megacolon

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Best=20 Therapy

Nonspecific Therapy=20

Most cases of acute diarrhea are self-limiting = and=20 require only nonspecific therapy geared toward replacing lost fluids = and=20 electrolytes

Rehydration = Therapy=20

Oral rehydration solution
- Dose: lowest effective single dose, 1 L/24 = hr; daily=20 max, 5 L
Intravenous fluid=20
- Dose: lowest effective single dose, 1 L/24 = hours;=20 daily max, 5 L
Intraluminal=20 Agents=20
- Adsorbents=20
  - Kaolin-pectin
    - Dose: lowest effective single dose, 15 = ml q.i.d.;=20 daily max, 240 ml
  - Bismuth subsalicylate=20
    - Dose: lowest effective single dose, 30 = ml; daily=20 max, 120 ml=20
    - Cost/15 days: $3
  - Psyllium=20
    - Dose: lowest effective single dose, 18 = g/24 hr;=20 daily max, 30 g/24 hr=20
    - Cost/22=9637 days: $11=20

Transit Inhibitors

Opiates=20
- Deodorized tincture of opium (morphine, 10 = mg/ml)=20
  - Dose: lowest effective single dose, 5 = drops=20 q.i.d.; daily max, 80 drops
- Paregoric (morphine, 0.4 mg/ml)=20
  - Dose: lowest effective single dose, 5 ml = q.i.d.;=20 daily max, 40 ml=20
  - Cost/6=9612 days: $86
- Morphine sulfate (20 mg/ml)=20
  - Dose: lowest effective single dose, 2 = drops=20 q.i.d.; daily max, 40 drops
- Codeine phosphate or sulfate=20
  - Dose: lowest effective single dose, 15 = mg q.i.d.;=20 daily max, 240 mg
- Diphenoxylate with atropine
  - Dose: lowest effective single dose, 2.5 = mg (1=20 tablet) t.i.d., p.o.; daily max, 20 mg (8 tablets)
  - Cost/10 days: $14 to $37 =
- Difenoxin with atropine=20
  - Dose: lowest effective single dose, 1 mg = (1=20 tablet) t.i.d., p.o.; daily max, 8 mg (8 tablets) =
- Loperamide (2 mg)=20
  - Dose: lowest effective single dose, 2 mg = t.i.d.;=20 daily max, 16 mg=20
  - Cost/10 days: $8 to $22 =
Others=20
- Clonidine
  - Dose: lowest effective single dose, 0.1 = mg p.o.,=20 t.i.d.; daily max, 0.9 mg
  - Cost/20 days: $12
- Octreotide injection=20
  - Dose: lowest effective single dose, 50 = =B5g p.o.,=20 t.i.d.; daily max, 600 =B5g=20

Therapy for=20 Specific Infections/Syndromes=20

Campylobacter Infection

Erythromycin=20
- Dose: lowest effective single dose, 250 mg = q.i.d.;=20 daily max, 500 mg q.i.d.=20
- Cost/10 days: $12
Fluoroquinolone
- Norfloxacin=20
  - Dose: lowest effective single dose, 400 = mg=20 b.i.d.=20
  - Cost/10 days: $78
- Ciprofloxacin=20
  - Dose: lowest effective single dose, 250 = mg b.i.d.;=20 daily max, 750 mg b.i.d.=20
  - Cost/10 days: $76 to $88 =
Azithromycin=20
- Dose: lowest effective single dose, 500 mg = to start,=20 then 250 mg daily=20
- Cost/5 days: $46 =

Salmonella enteritidis, S. = chlorerasius=20 Infection

Therapy should be reserved for severely ill = patients=20 or patients with compromised immunity=20
Fluoroquinolone=20
- Norfloxacin=20
  - Dose: lowest effective single dose, 400 = mg b.i.d.=20
  - Cost/10 days: $78
- Ciprofloxacin=20
  - Dose: lowest effective single dose, 250 = mg b.i.d.;=20 daily max, 750 mg b.i.d.
  - Cost/10 days: $76 to $88 =
Azithromycin=20
- Dose: lowest effective single dose, 500 mg = to start,=20 then 250 mg daily
- Cost/5 days: $46
Trimethoprim-sulfamethoxazole=20
- Dose: lowest effective single dose, = 160/800 mg=20 b.i.d.=20
- Cost/15 days: $9
Ampicillin=20
- Dose: lowest effective single dose, 250 mg = q.i.d.;=20 daily max, 500 mg b.i.d.=20
- Cost/10 days: $11 =

Shigella Infection=20

Fluoroquinolone=20
- Norfloxacin=20
  - Dose: lowest effective single dose, 400 = mg b.i.d.=20
  - Cost/10 days: $78
- Ciprofloxacin=20
  - Cost/10 days: $76 to $88 =
Azithromycin=20
- Dose: lowest effective single dose, 500 mg = to start,=20 then 250 mg daily
- Cost/5 days: $46 =

Clostridium difficile Infection=20

Metronidazole=20
- Dose: lowest effective single dose, 250 mg = q.i.d.;=20 daily max, 1,000 mg=20
- Cost/14 days: $28
Vancomycin=20
- Dose: lowest effective single dose, 125 mg = q.i.d.;=20 daily max, 2,000 mg=20
- Cost/15 days: $665 to $3,200=20

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Best References

Bricker E, et al: Cochrane Database Syst Rev=20 (1):CD004610, 2005 [PMID 15674956]

Guerrant RL, et al: Clin Infect Dis 32:331, = 2001 [PMID=20 11170940]

Schiller LR: Ailment Pharmacol Ther 9:87, 1995 = [PMID=20 7605866]

Schiller LR: Med Clin North Am 84:1259, 2000 = [PMID=20 11026928]

Thielman NM, et al: N Engl J Med 350:38, 2004 = [PMID=20 14702426]

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Chronic=20 Diarrhea=20

Lawrence R. Schiller, M.D., = F.A.C.P.
Baylor=20 University Medical Center

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best= =20 References=20

Definition/Key=20 Clinical Features

Frequent passage of loose stools for more = than 4=20 wk=20
Classified according to stool = characteristics (i.e.,=20 watery, inflammatory, or fatty)=20
- Blood and pus in stools are typical of = inflammatory=20 diarrhea, although a range of underlying inflammatory diseases = (e.g.,=20 inflammatory bowel disease, infections, ischemia, radiation = enteritis, and=20 neoplasia) may also produce watery, secretory diarrhea without = blood or=20 pus

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Differential=20 Diagnosis

Secretory Diarrhea

Bacterial toxins=20
Congenital syndromes=20
Ileal bile acid malabsorption=20
Microscopic colitis and other inflammatory = bowel=20 disease=20
Diverticulitis=20
Medications and toxins=20
Laxative abuse=20
Surgical complications (e.g., following = gastric=20 bypass, vagotomy, pyroplasty, bowel resection, ileostomy,=20 cholecystectomy)=20
Diabetes mellitus and associated=20 complications=20
Opportunistic infections or lymphoma = associated with=20 HIV=20
Neuroendocrine tumors=20
Idiopathic secretory diarrhea=20

Osmotic diarrhea=20

Carbohydrate malabsorption=20
Magnesium ingestion =

Inflammatory diarrhea

Invasive/ulcerating infections=20
Inflammatory bowel disease=20
Diverticulitis=20
Ischemia/radiation injury=20
Neoplasia

Fatty diarrhea

Malabsorption syndrome=20
- Mucosal diseases=20
- Short bowel syndrome=20
- Small bowel bacterial overgrowth=20
- Mesenteric ischemia
Maldigestion=20
- Pancreatic exocrine insufficiency =
- Bile acid = deficiency

Clinical Pearls

An important goal is to distinguish = between diarrhea=20 associated with irritable bowel syndrome (which is characterized = by=20 abdominal pain during defecation and altered bowel habits) and = diarrhea=20 associated with other functional or organic problems=20

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Best=20 Tests

Medical history=20
- A thorough and accurate medical history = is=20 essential and should elicit the following information:=20
  - Onset, pattern, and duration of = diarrhea=20
  - Stool characteristics (i.e., watery, = bloody,=20 fatty)=20
  - Long-term trends in body weight =
  - Current appetite and food = intake=20
  - Previous medical problems and = surgeries=20
  - Previous evaluations and = treatments=20
  - Clues pointing to other systemic=20 illnesses
Physical examination=20
- In addition to revealing the severity of = the=20 patient's condition, signs and symptoms should yield additional=20 etiologic clues=20
  - Characteristic skin changes indicative = of=20 mastocytosis, glucagonoma, Addison disease, amyloidosis, = carcinoid=20 syndrome, Degos disease, and celiac disease=20
  - Orthostatic hypotension and = hepatosplenomegaly=20 may be associated with amyloidosis=20
  - Hepatosplenomegaly, edema, right-sided = heart=20 murmur, and flushing may indicate carcinoid syndrome=20
  - Presence of arthritis may indicate = inflammatory=20 bowel disease, Whipple disease, or enteric infection=20
  - Absence of peripheral arterial pulses = or=20 presence of bruits may indicate mesenteric vascular = disease=20
  - Defective sphincter or pelvic muscle = floor=20 function, as revealed by rectal examination, is associated = with fecal=20 incontinence
Routine laboratory evaluation=20
- Stool analysis (i.e., sodium and = potassium=20 concentrations, osmolality, pH, electrolyte concentrations) = facilitates=20 categorization and should be obtained through a random sample or = timed=20 collection

Recommended=20 Evaluations Based on Stool Characteristics
Watery Secretory Diarrhea

Because of its broad differential = diagnosis, a=20 thorough evaluation is warranted and may include the following=20 tests:=20
- Stool culture: Can exclude = infection=20
- Biopsy of the small colon or = bowel: Used to=20 determine implicating pathogens in immunocompromised = patients=20
- Radiographic and endoscopic = testing: Should=20 be conducted to identify structural disease=20
- CT: Can detect small bowel and = colonic=20 disease=20
- Colonoscopic or sigmoidoscopic = evaluation of=20 the colonic mucosa: Essential to evaluate gross changes and = obtain=20 biopsy samples indicative of microscopic colitis syndrome =
- Serum peptide or urinary secretagogue = metabolite measures: Should be restricted to patients with = symptoms=20 consistent with tumor syndromes or in whom diagnosis is = uncertain=20 following initial testing=20
- A trial of bile acid=96binding = resins: Can be=20 used in patients with apparent idiopathic secretory diarrhea to=20 determine if bile acid malabsorption plays a role in the = patient's=20 condition

Watery Osmotic=20 Diarrhea=20

Low electrolyte concentrations indicate = that some=20 other substance, usually ingested magnesium or malabsorbed = carbohydrates,=20 is taking up osmotic space and holding water in the lumen=20
- Magnesium excretion of > 15 mmol = daily or=20 concentration > 45 mmol in a random stool sample is = indicative of=20 intentional or accidental magnesium-induced diarrhea=20
- Stool pH < 6 coupled with a thorough = dietary=20 history may reveal carbohydrate malabsorption
Other common causes of osmotic diarrhea = include=20 excessive fructose, poorly absorbed sugar alcohols (e.g., = sorbitol,=20 mannitol), and use of carbohydrate inhibitors (e.g., acarbose)=20

Chronic Inflammatory=20 Diarrhea=20

Endoscopic and radiographic evaluations = should be=20 conducted to determine the presence of structural problems: =
- Consider sigmoidoscopy or colonoscopy = first since=20 colitis is a common cause of inflammatory diarrhea; biopsies can = be=20 performed to categorize colitis=20
- CT scans often reveal inflammatory = changes in the=20 small bowel and colon and identify complications (e.g., = abscess)=20
Rule out infections that produce chronic = diarrhea by=20 culture, biopsy, or serologic testing, particularly in patients = with HIV=20 who are prone to opportunistic infections

Chronic Fatty Diarrhea=20

Because the common criteria to define = steatorrhea=20 (i.e., stool fat output > 7 g/24 hours or > 9% daily intake) = are=20 often invalid in patients with diarrhea, the threshold should be = corrected=20 for fat intake and estimated from diet diaries maintained during = timed=20 stool collection whenever possible=20
- Substitute qualitative estimation of fat = excretion=20 by Sudan stain of fecal smears when timed collection or = quantitative=20 analysis is impossible
Fecal fat concentration may provide a clue = to the=20 etiology of steatorrhea (e.g., low in mucosal disease, high in = pancreatic=20 exocrine insufficiency, lack of bile acids)=20
- Concentrations > 9.5g/100 g are = strong=20 indicators of pancreatic or biliary steatorrhea =
If the cause of steatorrhea remains = unclear,=20 evaluation of the absorptive surface of the small intestine by = endoscopic,=20 histologic, and radiographic tests is recommended=20
- If the absorptive surface is normal, = consider=20 luminal problems with fat solubilization or digestion=20

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Best=20 Therapy

Nonspecific Drug Therapy=20

Antidiarrheals, routine dosing (i.e., = scheduled=20 before mealtime or bedtime) is more effective than dosing =93as = needed=94 or=20 after passing stools=20
- Diphenoxylate with atropine
  - Dose: lowest effective single dose, = 2.5 mg (1=20 tablet) t.i.d., p.o.; daily max, 20 mg (8 tablets)=20
  - Cost/30 days: $42 to $111 =
- Difenoxin with atropine=20
  - Dose: lowest effective single dose, 1 = mg (1=20 tablet) t.i.d., p.o.; daily max, 8 mg (8 tablets) =
- Loperamide (2 mg)=20
  - Dose: lowest effective single dose, 2 = mg t.i.d.;=20 daily max, 16 mg=20
  - Cost/30 days: $24 to $66 =
Potent opiates, often underutilized in = patients=20 unresponsive to simple antidiarrheals=20
- Deodorized tincture of opium (10 mg=20 morphine/ml)=20
  - Dose: lowest effective single dose, 5 = drops=20 q.i.d.; daily max, 80 drops
- Paregoric (0.4 mg morphine/ml)=20
  - Dose: lowest effective single dose, 5 = ml q.i.d.;=20 daily max, 40 ml=20
  - Cost/6=9612 days: $86 =
- Morphine sulfate (20 mg/ml)=20
  - Dose: lowest effective single dose, 2 = drops=20 q.i.d.; daily max, 40 drops
- Codeine phosphate or sulfate=20
  - Dose: lowest effective single dose, 15 = mg=20 q.i.d.;daily max, 240 mg
Stool modifiers/intraluminal agents may be = of=20 special help in patients with concomitant fecal = incontinence=20
- Psyllium=20
  - Dose: lowest effective single dose, 18 = g/24 hr;=20 daily max, 30 g/24 hr=20
  - Cost/22=9637 days: $11=20

Therapy for = Specific=20 Syndromes
Osmotic = Diarrhea=20

Fasting or elimination of offending agent = from diet=20 will cause symptoms to abate unless other diarrhea-producing = mechanisms=20 are still active (e.g., short bowel syndrome, diseases of small = bowel=20 = mucosa)

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Best=20 References

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

Hasler WL: Dumping syndrome. Curr Treat = Options=20 Gastroenterol 5:139, 2002 [PMID 11879594]

Kalantzis N, et al: Hepatogastroenterology = 52:414, 2005=20 [PMID=20 15816447]

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

Schiller LR: Aliment Pharmacol Ther 9:87, = 1995 [PMID=20 7605866]

The author has received grants for = educational=20 activities from and served as an advisor for Novartis = Pharmaceuticals Corp.,=20 GlaxoSmithKline, Romark Laboratories, Salix Pharmaceuticals, Inc., = Santarus,=20 Inc., and Takeda Pharmaceuticals North America, Inc.; has received = grants=20 for clinical research from Novartis Pharmaceuticals Corp. and=20 GlaxoSmithKline; and has served as an advisor to TAP Pharmaceutical=20 Products, Inc.

March=20 = 2009

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