diarrhea%20in%20adults%20-%20chronic
DIARRHEA IN ADULTS - CHRONIC
Chronic diarrhea is defined as the abnormal passage of ≥3 loose or liquid stools per day for ≥4 weeks 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.
Categories include watery diarrhea (eg osmotic, functional or secretory), inflammatory diarrhea and fatty diarrhea.

Diarrhea%20in%20adults%20-%20chronic Diagnosis

History

A detailed medical history assists in:

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

Characteristics of Diarrhea

Duration and Pattern

  • Identify aggravating (eg diet, stress) and relieving factors (diet, over-the-counter and prescription drugs)
  • Diarrhea that is continuous or nocturnal and lasting <3 months is more likely due to an organic disease
  • Diarrhea occurring after meals is common in patients with IBS while diarrhea after a long period of constipation is seen with impaction with overflow diarrhea
  • 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

Associated Symptoms

  • Alarm symptoms include abdominal pain or discomfort, unintentional weight loss of >5 kg, GI bleeding and fever  
    • The absence of abdominal pain during defecation and presence of weight loss are points against the diagnosis of functional bowel syndrome, eg IBS
  • Other symptoms include bloating and flatulence which may indicate a malabsorption syndrome or food intolerance, nausea and vomiting (N/V) and dehydration

Stool Characteristics

  • Blood in the stool may be due to malignancy, inflammatory bowel disease (IBD), hemorrhoids or infection with invasive organisms
  • Tan or white-colored stool may suggest celiac disease
  • 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/caffeine consumption
  • Fiber intake
  • Raw seafood or shellfish
  • Milk products, including raw milk and lactose

Medical History

  • History of recurrent bacterial infections may point to a primary immunoglobulin deficiency
  • Previous surgery, pancreatic disease or radiation therapy, eg pelvic irradiation
    • 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, celiac disease, colitis, IBS, IBD, lactose intolerance 

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 magnesium (Mg)-containing products, antihypertensives, nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics may cause diarrhea
  • Recent antibiotic therapy may make a patient prone to Clostridioides difficile-associated diarrhea (please see Clostridioides difficile Infection disease management chart for further information)

History of Travel

  • Investigate possibility of exposure to infectious gastrointestinal (GI) pathogens, eg parasites and protozoa

Family History

  • Ask patient about a family history of inflammatory bowel, neoplastic or celiac disease, thyroid diseases or congenital diarrheal disorders

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, dry mouth, orthostatic changes in blood pressure, pulse
  • Look for signs of toxicity including fever and signs of nutrient malabsorption, eg muscle wasting, anemia, scars from previous abdominal surgery, impaired cognitive function 
  • Perform an abdominal exam to check bowel sounds and the presence of distension, tenderness or masses; a rectal exam (including a digital rectal exam) may show an abnormal sphincter tone suggesting fecal incontinence or anal fistulae suggesting Crohn's 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

INITIAL LABORATORY TESTS FOR CHRONIC DIARRHEA

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), vitamin B12, folate, ferritin, C-reactive protein (CRP)
  • Thyroid function tests

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 sodium and potassium 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 100 g/day 3 days before the specimen collection

Tests on Stool Water

  • The pH of stool water is often <6 in carbohydrate malabsorption resulting in carbohydrate fermentation; fecal pH test may be done in all patients presenting with fatty diarrhea
  • 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

FURTHER TESTS TO DETERMINE ETIOLOGY OF CHRONIC DIARRHEA

Stool Analysis

  • Mg, which may be ingested through laxatives, antacids and mineral supplements, may be measured in stool water through spectrophotometry
  • Fecal calprotectin and fecal lactoferrin
    • Considered as adjunctive tests in evaluating chronic diarrhea as levels are increased in intestinal inflammation and may help identify inflammatory causes
    • Threshold values of 50 μg/g for fecal calprotectin and 4-7.25 μg/g for fecal lactoferrin are used to optimize sensitivity for IBD

Stool Culture

  • Bacterial infections are seldom the cause of chronic diarrhea in immunocompetent patients
  • Clarify 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 and Cryptosporidium spp, microsporidia

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; used to rule out small bowel cancer and anatomic defects  
  • 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 IBD, tuberculosis (TB), intestinal lymphoma, carcinoid syndrome and other neuroendocrine tumors

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
    • Should be performed to confirm positive serologic test for celiac disease prior to placing a patient on a gluten-free diet

Serologic Tests

  • Serologic testing for celiac disease may be considered in populations with a high prevalence for this disorder
    • Tests include screening for IgA or IgG tissue transglutaminase and IgA or IgG deaminated gliadin peptides
  • 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 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

Breath Hydrogen Test

  • Used in evaluating patients for chronic osmotic diarrhea 
  • 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 Bile Acid Diarrhea

  • Total bile acid measured in a 48-hour stool collection identifies increased fecal bile acids 
  • Serum fibroblast growth factor 19 level measures a feedback defect in the synthesis of bile acids 
  • Selenium homotaurocholic acid test identifies patients with diarrhea caused by malabsorption of bile acids  
  • If above tests are not available, bile acid sequestrants can be empirically given to patients and clinical improvement  suggests a bile acid diarrhea

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 first 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 in the blood of excess vasoactive intestinal peptide, gastrin, calcitonin, glucagon, adrenocorticotropic hormone, and urinary metabolites of endocrine mediators (eg 5-hydroxyindole acetic acid, metanephrines) 

Categories of Chronic Diarrhea

  • 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

Watery Diarrhea

Osmotic Diarrhea

  • Water is retained due to substances that are poorly absorbed; stool osmotic gap is >125 mOsm/kg
    • Ingestion of exogenous Mg from Mg-containing antacids
    • Ingestion of laxatives
    • Ingestion of poorly absorbable carbohydrates,  eg lactase and fructose
    • Celiac disease

Functional Diarrhea   

  • A type of watery diarrhea that has hypermotility and small-volume stool (<350 mL/day); osmotic gap is within reference range of 50-125 mOsm/kg 
  • Responds to a modified diet low in fermentable carbohydrates and high in fiber, and improves at night and with fasting 
  • Often caused by IBS 
  • Diagnostic criterion includes watery or loose stools, without bothersome bloating or predominant abdominal pain in >25% of bowel movements for the last 3 months with symptoms starting at least 6 months prior to diagnosis (Rome IV) 
    • Should not include patients fulfilling the criteria for diarrhea-predominant IBS

Secretory Diarrhea

  • Reduced water absorption, stool volume >1 L/day, frequently occurs at night, and continues despite fasting; stool osmotic gap is <50 mOsm/kg
    • Small bowel bacterial overgrowth
    • Endocrine diarrhea, eg hyperthyroidism, Addison disease
    • Structural diseases, eg short bowel syndrome, IBD, tumors, gastrocolic or enteroenteric fistula, mucosal diseases
    • Peptide-secreting tumors, eg carcinoid syndrome, Zollinger-Ellison syndrome (ZES), glucagonoma
    • Medications: Antiarrhythmics, antibiotics, antihypertensives, antineoplastics, biguanides, Calcitonin, Colchicine, Digitalis, NSAIDs, prostaglandins, proton pump inhibitors, selective serotonin reuptake inhibitors, Ticlopidine 
    • Previous GI surgery

Inflammatory Diarrhea

  • Increased white cell count with occult or frank pus or blood
    • Invasive infections
    • Pseudomembranous colitis, IBD, ischemia, radiation enteritis
    • Neoplasm
    • The above conditions may produce a secretory diarrhea without inflammatory markers in the stool and therefore should be considered in the evaluation of secretory diarrhea as well

Fatty Diarrhea 

  • Abdominal distension and bloating with malodorous, large, floating, pale fatty stool
    • Maldigestion (inadequate luminal breakdown of triglyceride): Pancreatic exocrine insufficiency, inadequate luminal bile acid, eg primary biliary cholangitis (PBC)
    • Malabsorption (inadequate mucosal transport of the products of digestion): Celiac disease, Orlistat and Acarbose drugs, giardiasis
    • Small bowel bacterial overgrowth
    • Previous GI surgery
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