Evaluating the Patient with Chronic Unexplained Diarrhea: A Systematic Approach to Diagnosis and Tre

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Evaluating the Patient with Chronic Unexplained
Diarrhea A Systematic Approach to Diagnosis and
Treatment

• Charles J. Kahi, MD
• Assistant Professor of Clinical Medicine
• Indiana University School of Medicine

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Chronic Diarrhea A Clinical Challenge

• Common complaint to primary care physicians and
  gastroenterologists
• Complex differential diagnosis
• Wide variety of available tests
• Accurate diagnosis may be elusive
• Most recommendations for evaluation and therapy
  based on expert opinion (referral bias)
• Systematic ,common-sense approach yields answer
  in most cases ( gt 90)

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Is it Chronic? Is it Diarrhea?

• No consensus definition
• Four-week cutoff Most acute (infectious)
  diarrheas would have resolved 6-8 weeks better
  distinction
• Increased frequency of stool ( gt 3/day) is
  hallmark
• Most patients consider increased liquidity as
  essential feature
• Stool weight gt 200 g/day Not absolute criterion!
• Fecal incontinence Needs to be excluded and
  managed as incontinence, not diarrhea

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Differential Diagnosis (1)

• Watery Diarrhea
• Osmotic diarrhea
• - Osmotic laxatives
• - Carbohydrate malabsorption - Endocrine
  diarrhea Hyperthyroidism
• Secretory diarrhea Addisons disease
• - Congenital syndromes (chloridorrhea)
  Gastrinoma
• - Bacterial toxins VIPoma
• - Ileal bile acid malabsorption
  Somatostatinoma
• - Inflammatory bowel disease Carcinoid
  syndrome
• Ulcerative colitis Medullary carcinoma
  thyroid
• Crohns disease Mastocytosis
• Microscopic colitis Pheochromocytoma
• Lymphocytic colitis - Other tumors
• Collagenous colitis Colon carcinoma
• - Diverticulitis Lymphoma
• - Drugs and poisons Villous adenoma
• - Laxative abuse (stimulant laxatives) -
  Idiopathic secretory diarrhea
• - Disordered motility/regulation Epidemic
  (Brainerd)
• Postvagotomy diarrhea Sporadic
  Postsympathectomy diarrhea

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Differential Diagnosis (2)

• Inflammatory diarrhea Fatty diarrhea
• - Inflammatory bowel disease - Malabsorption
  syndromes
• Ulcerative colitis Mucosal diseases (celiac
• Crohns disease disease, Whipples)
• Diverticulitis Short-bowel syndrome
• Ulcerative jejunoileitis Small bowel
  bacterial overgrowth
• - Infectious diseases Mesenteric ischemia
• Pseudomembranous colitis - Maldigestion
• Invasive bacterial infections Pancreatic
  exocrine insufficiency
• (TB, yersiniosis) Inadequate luminal bile
  acid
• Ulcerating viral infections (CMV, HSV)
  concentration
• Invasive parasitic infections
• (amebiasis, strongyloidiasis)
• - Ischemic colitis
• - Radiation colitis
• - Neoplasia
• Colon carcinoma
• Lymphoma

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Medications and toxins associated with diarrhea

• Antibiotics
• Antiretroviral agents
• Antineoplastic agents
• Anti-inflammatory agents (NSAIDs, gold, 5-ASA)
• Antiarrhythmics (quinidine)
• Antihypertensives (ß blockers)
• Oral hypoglycemics (metformin, acarbose)
• Antacids (magnesium-containing)
• Acid-reducing agents (H2 blockers, PPIs)
• Colchicine
• Prostaglandin analogs (misoprostol)
• Theophylline
• Vitamin and mineral supplements
• Herbal products
• Heavy metals

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Practical approach
Secretory
Osmotic
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History

• Define patients complaint of diarrhea (change in
  consistency, presence of urgency or incontinence)
• Stool characteristics (blood, mucus, oil, pus,
  food particles) and volume
• Duration, pattern of onset
• Relation to prandial state
• Nocturnal diarrhea
• Weight loss
• Travel history
• Risk factors for HIV infection
• Dietary profile and medication review
• Family history of IBD
• Other systemic symptoms

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Physical examination

• More helpful to determine severity rather than
  etiology
• Hemodynamics, temperature, signs of toxicity
• Helpful clues

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Stool Analysis

• Directed testing for confirmation based on
  clinical suspicion, or broad net cast in
  difficult cases
• Categorize diarrhea into watery, inflammatory,
  fatty
• Timed collection is best, spot tests on random
  stool sample more practical
• - Occult blood
• - White blood cells
• - pH
• - Sudan stain for fat
• - Cultures
• - Laxative screen
• - Electrolytes, osmolality

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Stool Analysis

• Occult blood and white blood cells
• - Primarily define inflammatory diarrhea
• - Wright stain Sensitivity 70, specificity 50
  for leukocytes
• - Fecal calprotectin and lactoferrin less
  operator dependent, but test characteristics in
  chronic diarrhea not well defined
• pH
• - Low pH (lt 6) generally indicative of
  carbohydrate malabsorption
• Sudan stain
• - Fatty diarrhea (steatorrhea)
• - Gold standard Quantitative estimation of
  stool fat on collected specimen
• - Qualitative estimation feasible on random
  sample,
• - Semiquantitative methods (number and size of
  fat globules) correlate well with quantitative
  collection

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Stool Analysis

• Stool cultures
• - Infection Usually inflammatory diarrhea
• - Bacterial infection rarely cause of chronic
  diarrhea in immunocompetent host - Routine
  cultures are low yield and not recommended (but
  done anyway!)
• - Special techniques for Aeromonas and
  Plesiomonas
• - Ova and Parasites
• - Always consider giardiasis (stool ELISA for
  Giardia antigen)
• Laxative screen
• - High index of suspicion
• - Stool for bisacodyl and phenolphtalein, urine
  for anthraquinones
• - Confirm on another sample before confronting
  patient

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Stool Analysis

• Stool electrolytes
• Stool osmotic gap 290 2(Na K)
• - Gap lt 50 mOsm/Kg Pure secretory diarrhea
• - Gap gt 125 mOsm/Kg Pure osmotic diarrhea
• - Gap 50-125 mOsm/kg Mixed or mild carbohydrate
  malabsorption
• Measured stool osmolality
• - Not used to calculate gap
• - Useful in cases of unexplained diarrhea
• - Low measured stool osmolality (lt 290 mOsm/Kg)
  suggestive of contamination with water or dilute
  urine

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Chronic Watery Secretory Diarrhea
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Chronic Watery Secretory Diarrhea

• Exclude giardiasis
• All patients who undergo sigmoidoscopy or
  colonoscopy should have biopsies obtained to
  exclude microscopic colitis
• Colonoscopy preferred Intubation of terminal
  ileum, screening for neoplasia, right-sided
  disease (collagenous colitis)
• Sigmoidoscopy reasonable first test otherwise
• Upper endoscopy with small bowel biopsies to
  exclude celiac sprue
• Small bowel radiographs, WCE IBD, tumors,
  fistula, short-bowel syndrome
• CT scan to assess small and large bowel, and
  pancreas
• Endocrine diarrhea RARE, even among patients
  with chronic diarrhea
• Screening with peptide panels unhelpful due to
  high false-positive rate
• Bile acid malabsorption Controversial
• Trial of bile acid sequestrant reasonable
  diagnostic/therapeutic step

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Chronic Watery Osmotic Diarrhea

• Magnesium ingestion
• - Stool concentration gt 90 meq/L
• - Intentional (laxative abuse) or accidental
  (antacids, mineral supplements)
• Carbohydrate malabsorption
• - Lactase deficiency
• - Fructose intolerance (high fructose corn
  syrup)
• - Sugar alcohols used as artificial sweeteners
  (sorbitol, mannitol)

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Chronic Inflammatory Diarrhea

• Important considerations
• - IBD
• - Infection (C. difficile, CMV, TB, amebiasis)
• - Ischemia
• - Radiation enteritis
• - Neoplasia
• Conditions may produce watery secretory diarrhea
• Diagnosis Radiographic and endoscopic techniques

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Chronic Fatty Diarrhea

• Steatorrhea usually defined as loss of fat of gt 7
  g per 24 hours however 7-14 g range has poor
  specificity
• Test may be compromised by orlistat and olestra
• Three major causes
• 1. Pancreatic exocrine insufficiency (chronic
  pancreatitis)
• 2. Mucosal diseases (celiac sprue, small bowel
  bacterial overgrowth)
• 3. Lack of bile (advanced primary biliary
  cirrhosis)
• Clue Fecal fat concentration
• - Concentration gt 9.5 g per 100 g suggestive of
  pancreatic or biliary cause
• Exclude mucosal disease first, then evaluate
  pancreas (CT, MRCP, EUS)
• Elderly, B12 deficiency, low albumin, previous
  partial gastrectomy, small bowel diverticula
  Suspect Small bowel bacterial overgrowth
• Pancreatic function tests not commonly used
• Empiric trial of pancreatic enzyme
  supplementation

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Empiric Therapy of Chronic Diarrhea
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Irritable Bowel Syndrome

• Rome Criteria
• Recurrent abdominal pain or discomfort at least
  3 days per month for the past 3 months,
  associated with 2 or more of
• - Improvement wih defecation
• - Onset associated with a change in frequency
  of stool
• - Onset associated with a change in form
  (appearance) of stool
• Periods of constipation common
• Long history, passage of mucus, exacerbation by
  stress
• Diarrhea during waking hours, urgency
• Coexistence with other functional disorders
• Against IBS Recent onset, nocturnal diarrhea,
  bleeding, weight loss, voluminous or greasy
  stool, abnormal blood tests
• Rule out celiac sprue!
• Functional diarrhea Recurrent loose stools
  without pain.

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Additional reading

• Fine KD and Schiller LR. AGA technical review
  Evaluation and management of chronic diarrhea.
  Gastroenterology 1999 1161464.
• Mayer EA. Irritable Bowel Syndrome. NEJM 2008
  3581692.
• Singh VV, Toskes PP. Small bowel bacterial
  overgrowth presentation, diagnosis, and
  treatment. Curr Treat Options Gastroenterol 2004
  719.
• Gibson PR et al. Fructose malabsorption and the
  bigger picture. Aliment Pharmacol Ther 2007
  25349.
• Stroehlein JR. Microscopic colitis. Curr Opin
  Gastroenterol 1004 2027.