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DIARRHEA IN ADULTS - CHRONIC
Chronic diarrhea is defined as the abnormal passage of ≥3 loose or liquid stools per day for ≥4 week with or without a daily stool weight >200 g/day.
The definition of chronic diarrhea based on symptoms alone will lead to an overlap with functional bowel disorders eg irritable bowel syndrome.
Diarrhea that is continuous or nocturnal and lasting <3 months is more likely due to an organic disease.
The absence of abdominal pain during defecation and presence of weight loss are points against the diagnosis of functional bowel syndrome eg irritable bowel syndrome.

Diagnosis

  • Stool frequency, consistency and volume can aid in categorization
  • Some categories overlap; thus, it is prudent to first categorize the type of diarrhea before a full diagnostic evaluation and treatment as this narrows down the differential diagnoses and reduces unnecessary testing

History

A detailed medical history assists in:

  • Categorizing symptoms as being more likely due to an organic vs a functional cause
  • Determining specific causes of diarrhea
    • Differentiating malabsorptive diarrhea from colonic or inflammatory diarrhea

Characteristics of Diarrhea

Duration and Pattern

  • Diarrhea that is continuous or nocturnal and lasting <3 months is more likely due to an organic disease
  • Diarrhea should be differentiated from fecal incontinence
    • Many patients do not volunteer incontinence as a symptom and will instead describe it to the doctor as diarrhea
  • Identify aggravating (eg diet, stress) and relieving factors (diet, over-the-counter and prescription drugs)

Associated Symptoms

  • The absence of abdominal pain during defecation and presence of weight loss are points against the diagnosis of functional bowel syndrome [eg Irritable bowel syndrome (IBS)]

Stool Characteristics

  • Blood in the stool may be due to malignancy, inflammatory bowel disease (IBD), hemorrhoids or infection with invasive organisms
  • Food particles or oil in the stool may be due to malabsorption, maldigestion or a decreased intestinal transit time
  • Watery stools imply an osmotic or secretory process
  • Voluminous, watery diarrhea suggests a disorder of the small bowel or proximal colon
  • Frequent, small-volume diarrhea may be associated with the colon or rectum

Pertinent Points in the History

Patient’s Diet

  • Ingestion of large amounts of poorly absorbable carbohydrates (eg sorbitol, mannitol and fructose which may be present in fruit juices, soft drinks, diet candies)
  • Excess coffee consumption
  • Fiber intake
  • Raw seafood or shellfish
  • Milk products

Medical History

  • History of recurrent bacterial infections may point to a primary immunoglobulin deficiency
  • Previous surgery, pancreatic disease or radiation therapy
  • Extensive resections of the ileum and right colon may substantially decrease absorptive capacity of surface, resulting in fat and carbohydrate or bile acid malabsorption and decreased transit time
  • Cholecystectomy may decrease transit time, bile acid malabsorption and increase enterohepatic cycling of bile acids
  • The following may predispose to diarrhea via different mechanisms:
    • Thyrotoxicosis, parathyroid disease, diabetes mellitus (DM), adrenal disease, systemic sclerosis

Intake of Drugs or Alcohol

  • Alcohol abuse may result in decreased transit time, decreased pancreatic function and decreased activity of intestinal disaccharidases
  • Investigate intake of prescription drugs and over-the-counter medicines including herbal therapy and supplements
    • Drugs such as Mg-containing products, antihypertensives, nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics may cause diarrhea
  • Recent antibiotic therapy may make a patient prone to Clostridium difficile-associated diarrhea (See Clostridium difficile Infection Management Chart)

History of Travel

  • Investigate possibility of exposure to infectious gastrointestinal (GI) pathogens

Family History

  • Ask patient about a family history of neoplastic, celiac or inflammatory bowel disease

Social History

  • Drinking water source
  • Sexual preference and activity [risk factors for human immunodeficiency virus (HIV) infection]
  • Patient’s occupation, area of residence

Physical Examination

Physical findings are usually more useful in establishing the severity of diarrhea than in determining its etiology

  • Assess patient’s volume status (eg skin appearance, orthostatic changes in blood pressure, pulse)
  • Look for signs of toxicity including fever and signs of nutrient malabsorption (eg wasting, anemia, scars from previous abdominal surgery)
  • Perform an abdominal exam to check bowel sounds and the presence of distension, tenderness or masses; a rectal exam may show an abnormal sphincter tone suggesting fecal incontinence or anal fistulae suggesting Crohn disease
  • Check for findings consistent with systemic diseases that may present with chronic diarrhea [eg tremor and exophthalmos in hyperthyroidism, lymphadenopathy in acute immune deficiency syndrome (AIDS), etc]

Laboratory Tests

In cases when findings from history and physical exam point to a particular diagnosis, it may be practical to proceed immediately to confirmatory tests for the specific disorder

Blood Tests

  • Complete blood count (CBC) to check for anemia and leukocytosis
  • Erythrocyte sedimentation rate (ESR)
  • Chemistries: Protein/globulin, albumin, urea, serum electrolytes, calcium
  • Others: Liver function tests (LFTs), Vit B12, folate, ferritin, C-reactive protein
  • Thyroid function tests
  • Serological tests for celiac disease
    • Celiac disease is prevalent in certain parts of the world ie western hemisphere
    • Tests include screening for IgA antiendomysium antibodies or anti-tissue transglutaminase antibodies

Stool Tests

Inspection of the Stool

  • May be done during rigid sigmoidoscopy without bowel preparation or
  • Stool collection over 24-48 hours or random sample

Stool Microscopy

  • Examine for ova and parasites

Stool Weight

  • May provide best information to the potential metabolic impact of diarrhea
  • May limit unnecessary tests if values <200 g/day are obtained

Stool Osmolality and Osmotic Gap

  • Measurement of stool Na and K concentrations allows calculation of the osmotic gap in stool water; normal fecal osmolality is 290 mOsm/kg
    • A small osmotic gap is characteristic of secretory diarrhea
    • A large osmotic gap is characteristic of osmotic diarrhea
  • A low stool osmolality may be due to contamination of the stool sample by the addition of water or dilute urine or by the ingestion of large amounts of hypotonic fluid

Stool Fat

  • Fat excretion >14 g in 24 hours points to a high probability of defective fat absorption
  • For the test to be valid, patients should have a fat intake of 70-100 g/day a few days before the specimen collection

Tests on Stool Water

  • The pH of stool water is often <6 in carbohydrate malabsorption resulting in carbohydrate fermentation
  • In cases where there is a high index of suspicion of factitious diarrhea due to surreptitious laxative use, stool water may be analyzed for laxatives using chemical or chromatographic tests

Stool Occult Blood and Leukocytes

  • Presence of occult blood or leukocytes may help identify inflammatory diarrhea

Stool Analysis

  • Mg which may be ingested through laxatives, antacids and mineral supplements may be measured in stool water through spectrophotometry
  • Low pH may suggest carbohydrate malabsorption
  • Fecal calprotectin is a Ca and Zn-binding protein from monocytes and neutrophils
    • Considered as an adjunctive test in evaluating chronic diarrhea as fecal calprotectin levels are increased in intestinal inflammation and may help identify inflammatory causes

Stool Culture

  • Bacterial infections are seldom the cause of chronic diarrhea in immunocompetent patients
  • Clarify human immunodeficiency virus (HIV) status of patient because persons with HIV-AIDS are more likely to have an infectious cause for chronic diarrhea
  • Infection should still be excluded by culture and special tests for other organisms
  • Organisms which may cause infectious chronic diarrhea include protozoa [eg Giardia and Entamoeba spp, Aeromonas, Plesiomonas, Candida spp; parasites eg Strongyloides, Cryptosporidium spp, microsporidia]

Endoscopy and Histology

  • Endoscopic investigation is warranted if patient is unresponsive to therapy, symptoms are persistent, and if diagnosis is inconclusive
  • Full colonoscopy should be done in the following cases:
    • If there is significant weight loss
    • Presence of occult/gross bleeding suggesting malignancy
    • When abnormal terminal ileum or proximal colon has been seen on radiograph 
    • In patients >50 years old for screening purposes
  • Endoscopy or enteroscopy is used to visualize the small bowel and colon and to do a directed biopsy
  • Flexible sigmoidoscopy is typically sufficient for patients <45 years old with chronic diarrhea and/or atypical symptoms
  • Colonoscopy with ileoscopy is recommended for patients >45 years old with chronic diarrhea
  • Random biopsy samples should be taken from several locations, including normal areas, to give the pathologist a greater chance of establishing the diagnosis

Small Bowel Biopsy and Aspirate

  • Cultures of small bowel aspirates are the most sensitive test for small bowel bacterial overgrowth; however, they may not reflect clinically significant overgrowth
  • Small bowel biopsies may establish diffuse mucosal diseases that give rise to malabsorption

Breath H2 Test

  • An increase in breath hydrogen concentration represents bacterial fermentation and indicates that unabsorbed carbohydrate (eg fructose, sucrose) has reached the colon
  • Tests may use lactose, glucose, lactulose and d-xylose
  • Provides only supportive evidence of the diagnosis

Tests for Lactase Deficiency

  • Lactase activity decreases rapidly in most non-Caucasian populations after the age of 2 years and lactase deficiency is considered normal in these populations
  • Lactase deficiency can be diagnosed by lactose hydrogen breath tests and lactose tolerance tests

Serologic Tests

  • Serologic testing for celiac sprue may be considered in populations with a high prevalence for this disorder
  • Other serologic tests may include detection of antibodies to Entamoeba histolytica for amoebiasis, fecal antigen for giardiasis, antibodies to HIV for HIV/AIDS and antinuclear antibody in conditions (eg scleroderma, vasculitis, hypothyroidism)

Tests for Pancreatic Exocrine Insufficiency

  • Tests include secretin test, bentiromide test, fecal elastase and stool chymotrypsin activity
  • Fecal elastase testing is reliable and convenient, and may be a good 1st choice in patients in whom chronic diarrhea is thought to be of pancreatic origin
    • Only reliable in moderate/severe pancreatic disease with poor sensitivity for mild disease
  • Endoscopic retrograde cholangiopancreatography (ERCP) has the greatest sensitivity for diagnosis of pancreatic ductal changes
  • Magnetic resonance cholangiopancreatography (MRCP) may be as sensitive as ERCP for detecting chronic pancreatitis and pancreatic cancer

Tests for Peptide-Secreting Tumors

  • Diarrhea due to hormone-secreting tumors is very rare
  • Testing is only recommended for patients with high-volume watery diarrhea and only when other causes have been excluded
  • Testing may involve detection of excess vasoactive intestinal peptide, gastrin, calcitonin, glucagon and urinary metabolites of endocrine mediators

Imaging

Bowel Imaging

  • Radiography of the stomach and colon may be complementary to endoscopy and colonoscopy because barium-contrast radiographs can detect fistulas and strictures better
  • Small bowel imaging with barium follow through or enteroclysis should be reserved for patients where malabsorption is suspected and distal duodenal histology is normal
  • Mesenteric angiography may show evidence of rare cases of intestinal ischemia due to vasculitis or atherosclerosis
  • Computed tomography (CT) scan may be used for the following:
    • To examine the pancreas for cancer or chronic pancreatitis
    • To detect inflammatory bowel disease (IBD) , tuberculosis (TB), intestinal lymphoma, carcinoid syndrome and other neuroendocrine tumors
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