Basics
Description
- Diarrhea, defined as stool output >200 g/24 h in children and adults or 10 g/kg/24 h in infants, that has occurred for >30 days
- Can be characterized by pattern of stool output with regard to the following:
- Volume
- Frequency
- Consistency
- Gross appearance
- Should be differentiated from acute diarrhea, which is generally caused by enteric pathogens, is self-limiting, and has a duration of symptoms <14 days; as well as persistent diarrhea, which lasts 14-29 days
Epidemiology
- Gender and genetic factors do not play a significant role in most cases of chronic diarrhea.
- Chronic diarrhea seen in the tropics and developing countries is more likely infectious in nature than in the United States.
Pathophysiology
The major categories are osmotic and secretory. Inflammatory and motility disorders are important subcategories to consider.
- Osmotic diarrhea occurs when unabsorbable solute accumulates in the lumen of the small intestine and colon, increasing intraluminal osmotic pressure and resulting in excessive fluid and electrolyte losses in stool.
- Osmotic diarrhea will improve with fasting.
- Osmotic diarrhea is usually related to malabsorption of dietary products or to the presence of congenital or acquired disaccharidase deficiency or glucose-galactose defects.
- Secretory diarrhea occurs when the net secretion of fluid and electrolyte is in excess of absorption in the intestine:
- Secretory diarrhea occurs independently of the osmotic load in the intestinal lumen and does not improve with fasting.
- The mechanisms for secretory diarrhea include the activation of intracellular mediators such as cAMP, cGMP, and calcium-dependent channels.
- These mediators stimulate active chloride secretion from the crypt cells and inhibit the neutral coupled sodium chloride absorption.
- Inflammation in the intestine can cause an alteration in mucosal integrity resulting in exudative loss of mucus, blood, and/or protein. Increased permeability and altered mucosal surface area may affect absorption and result in diarrhea due to malabsorption.
- Motility disorders affect intestinal transit time. Hypomotility can allow stasis from bacterial overgrowth and can lead to diarrhea.
Diagnosis
History
- Evaluation of the stool pattern, including consistency, frequency, and appearance
- The characteristics of the onset of diarrhea should be noted as precisely as possible (e.g., congenital, abrupt, or gradual).
- Overall duration of the diarrhea and pattern of intermittent versus continuous may also help in determining the underlying process.
- Stool characteristics should be investigated. Specifically:
- A history of blood and mucus in stool is strongly suggestive of inflammation.
- Large-volume stools (>750 mL/24 h) imply small bowel disease and/or a secretory process.
- Watery stools tend to be more associated with carbohydrate malabsorption, small bowel processes, medications, and functional processes.
- Steatorrhea (fatty stools) can be greasy, oily, foul-smelling, and bulky and are usually associated with pancreatic disease, bacterial overgrowth, and short bowel syndrome.
- Epidemiologic factors (e.g., travel before onset of illness, antibiotic exposure, and illness in other family members) should be elicited.
- Dietary intake including the types of food and the occurrence of diarrhea in close relationship to specific foods (e.g., dairy products) may be diagnostic. The amount and type of liquid ingested may also be helpful in diagnosis.
- Nutritional status and growth parameters should be assessed. The presence of growth failure or malnutrition has considerable implications compared with a child with normal growth and no history of weight loss.
- Exposure to medications (antibiotics, laxatives, chemotherapeutic agents) or herbal therapies
- Iatrogenic causes of diarrhea should be investigated by obtaining a detailed medication history and history of radiation therapy and surgery.
- Other symptoms associated with the diarrhea are important to assess and include abdominal pain, fever, bloating, tenesmus, soiling, rashes, and joint complaints.
- The presence or absence of abdominal pain should be evaluated. Pain is often present in patients with inflammatory bowel disease, irritable bowel syndrome, and mesenteric ischemia.
- Family history (e.g., celiac disease, inflammatory bowel disease, cystic fibrosis, and other pancreatic processes)
- Previous evaluation should be reviewed whenever possible, objective records should be examined before new studies are ordered.
Physical Exam
- Nutritional status: Compare height, weight, and head circumference with normal standards and previous exam measurements.
- Anthropometric measurements are important in assessing loss of body fat and muscle mass.
- Peripheral edema, ascites, rash, dystrophic nails, alopecia, chronic chest findings, and pallor may all be indicative of nutritional deficiencies secondary to chronic diarrhea.
- A rectal exam may reveal stool impaction with overflow diarrhea:
- Is there blood in the stool?
- Perianal disease (fistula, skin tags, abscess)
- Evidence of infection should be considered with symptoms such as fever, bloody diarrhea, and vital sign instability.
- Aphthous lesions, arthritis, and clubbing
- The abdominal exam in most patients is generally nonspecific.
- Other features of diagnostic significance include rashes on the skin, mouth ulcers, thyroid masses, wheezing, arthritis, heart murmurs, hepatomegaly or abdominal masses.
Diagnostic Tests & Interpretation
Lab
- Stool samples
- Stool should be cultured for bacteria, ova and parasites, and viral organisms.
- Clostridium difficile toxins A and B are heat-labile, and stool must be kept cool during transport.
- Collect stool in the correct containers to ensure accurate and reliable analysis.
- Stool samples can be tested for occult blood and for the presence of fecal leukocytes.
- Stool pH and reducing substances
- If stool is positive for reducing substances and/or the pH is <5.5, carbohydrate malabsorption with or without proximal small bowel injury is likely.
- Note: Sucrose is not a reducing substance. If sucrose malabsorption is suspected, stool sample has to be hydrolyzed with hydrochloric acid and heat before analysis.
- A positive Sudan stain of the stool is indicative of fat malabsorption. However, a 72-hour fecal fat collection remains the gold standard to diagnose fat malabsorption.
- Stool for fecal elastase can be used to assess fat malabsorption.
- Stool may be collected for electrolyte and osmolality measurements. Osmotic gap >100 mOsm/kg is indicative of an osmotic diarrhea.
- Spot or 24-hour collection for fecal α1-antitrypsin can help assess protein loss.
- Stool collection for fecal calprotectin to assess for IBD-protein found in neutrophils that enter the bowel during an inflammatory process
- CBC
- Hemoglobin and RBC may provide evidence and characteristics of anemia (i.e., microcytotic, macrocytotic, normochromic).
- Leukocytosis suggest the presence of inflammation.
- Eosinophilia can be seen with neoplasm, allergy, collagen vacular disease, parasitic infection, and eosinophilic gastroenteritis, or colitis.
- Other blood tests:
- Prealbumin and albumin can provide parameters of protein and overall nutritional status.
- Erythrocyte sedimentation rate and C-reactive protein (CRP) can serve as markers for inflammatory conditions.
- Hormonal studies to assess for secretory tumors (vasoactive intestinal peptide [VIP], gastrin, secretin, urine assay for 5-HT)
- In the evaluation for celiac disease, serum antitissue transglutaminase antibody and antiendomysial antibodies (presuming a normal level of total serum IgA)
- Hepatic panel, coagulation profile, and fat-soluble vitamin levels (25-OH vitamin D; vitamins E, A, K) may be helpful to assess fat malabsorption.
- Viral serologies such as HIV and cytomegalovirus need to be considered in the immunocompromised host with diarrhea.
- Thyroid studies in patients with large-volume watery diarrhea
- Specialized studies:
- A d-xylose absorption test is helpful in screening for small bowel injury. Timed serum d-xylose following oral ingestion is significantly lower in diseases causing diffuse mucosal damage to the small bowel (i.e., postviral enteropathy, celiac disease).
- A hydrogen breath test may be helpful in evaluating for the possibility of small bowel bacterial overgrowth.
- Sweat chloride if cystic fibrosis is suspected
Imaging
- Plain radiograph studies usually not helpful; may demonstrate presence or absence of formed stool and/or fecal impaction
- Upper GI series with small bowel follow-through may show partial small bowel obstruction, strictures, or evidence of inflammatory bowel disease.
- Abdominal CT scan may help in assessing the pancreas for calcifications and inflammation.
Diagnostic Procedures/Other
- Endoscopy with small bowel biopsy and small bowel aspirate for culture to help diagnose certain congenital, immunologic, or infectious causes of diarrhea
- Small bowel disaccharidase studies will help detect carbohydrate malabsorption.
- Colonoscopy will diagnose colitis related to inflammatory bowel disease or infection.
- Video capsule endoscopy may also be used to further evaluate the small bowel for evidence of inflammation.
Differential Diagnosis
- Infants (<1 year of age)
- Cow's milk and/or soy protein intolerance
- Intractable diarrhea of infancy is associated with diffuse mucosal injury beginning at <6 months of age, resulting in malabsorption and malnutrition (sucrose and lactase deficiency).
- Infectious/protracted postinfectious diarrhea
- Microvillus inclusions disease
- Tufting enteropathy
- Autoimmune enteropathy
- IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
- Congenital glucose-galactose malabsorption
- Hirschsprung disease with enterocolitis
- Transport defects (e.g., congenital chloridorrhea)
- Nutrient malabsorption (e.g., congenital glucose-galactose malabsorption and congenital lactase deficiency, sucrase-isomaltase deficiency)
- Cystic fibrosis
- AIDS enteropathy
- Primary immune defects
- Munchausen syndrome by proxy (factitious)
- Drug-, toxin-induced
- Children (1-5 years of age)
- Chronic nonspecific diarrhea of infancy (toddler's diarrhea)
- Infectious/postinfectious enteritis
- Giardiasis
- Eosinophilic gastroenteritis
- Sucrase-isomaltase deficiency
- Tumors (neuroblastoma, VIPoma with secretory diarrhea)
- Inflammatory bowel disease
- Celiac disease
- Cystic fibrosis
- Small bowel bacterial overgrowth
- AIDS enteropathy
- Constipation with (overflow) encopresis
- Acquired short bowel syndrome
- Shwachman syndrome
- Factitious
- Children (>5 years of age)
- Similar to above
- Acquired lactose deficiency (early adolescent)
- Inflammatory bowel disease
- Celiac disease
- Constipation with (overflow) encopresis
- Irritable bowel syndrome (adolescent)
- Laxative abuse (adolescents)
- Infection
- Bacterial (Aeromonas, Plesiomonas, Campylobacter, Salmonella, Mycobacterium tuberculosis, Yersinia, recurrent C. difficile)
- Viral (rotavirus, adenovirus, Norwalk virus, Norovirus)
- Parasites (Amoeba, Trichuris, Cryptosporidium, Giardia, Schistosoma, Cyclospora)
- Small bowel bacterial overgrowth
- Tumors (neuroblastoma, VIPoma with secretory diarrhea)
- Primary bowel tumors (rare, adolescent)
- Complex congenital heart disease with protein-losing enteropathy
- Pancreatic insufficiency/chronic pancreatitis
- Hyperthyroidism
- Diabetes
Treatment
Medication
- Presuming no inflammation or constipation, the use of antimotility agents such as loperamide and Lomotil, and antisecretory agents, such as octreotide, may have a role in noninfectious causes of diarrhea. However, identification and treatment of the underlying cause of diarrhea is always preferable.
- Pancreatic enzymes may be used in specific patients.
- Luminal (nonabsorbed) antibiotics for small bowel bacterial overgrowth
Alert
- In certain cases in which the diet is altered as a therapeutic intervention, the physician must ensure that the patient is still absorbing adequate calories and micronutrients, so that the nutritional status of the patient is not further compromised.
- Avoid the reinstitution of a regular diet too quickly following a severe and/or protracted insult to the gut because this may further exacerbate the diarrhea.
- The use of antimotility and antisecretory agents should be judicious and as an adjunct to other therapy but not as the mainstay in the treatment regimen.
- In patients with cow's milk and/or soy allergy, rechallenge after 12 months of age in a controlled environment in case anaphylaxis occurs.
- Children with the following symptoms should see a health care provider:
- Signs of dehydration
- Failure to thrive
- Diarrhea for more than 24-48 hours
- A fever of 102 °F or higher
- Stools containing blood or pus
- Stools that are black and tarry
Additional Treatment
- The first goal is to ensure adequate hydration status, nutritional intake, and to permit normal growth and development.
- Antibiotics when infection is suspected
- Many causes of congenital diarrhea do not have specific therapy available, and treatment is supportive.
- Diet: If infection is severe or protracted, an elemental formula may be necessary early in the recovery phase. If oral nutrition appears inadequate, the formula can be given in a slow, continuous fashion via a nasogastric/jejunal tube. Remove offending agent (e.g., cow's milk protein, soy protein, lactose, or gluten).
- In cases in which there is increased motility and thus rapid transit time, such as in chronic nonspecific diarrhea, alterations in the diet can be very helpful.
- Elimination of sorbitol-containing juices, which increases the osmotic load, and low-carbohydrate diet will help to lower the osmotic load delivered to the intestine. Furthermore, a high-fat diet will slow the intestinal transit time and increase the time available to absorb fluid, electrolytes, and nutrients from the intestinal tract.
Additional Reading
- Bhutta ZA, Nelson EA, Lee WS, et al. Recent advances and evidence gaps in persistent diarrhea. J Pediatr Gastroenterol Nutr. 2008;47(2):260-265. [View Abstract]
- Lee SD, Surawicz CM. Infectious causes of chronic diarrhea. Gastroenterol Clin North Am. 2001;30(3):679-692. [View Abstract]
- Pawlowski SW, Warren CA, Guerrant R. Diagnosis and treatment of acute or persistent diarrhea. Gastroenterology. 2009;136(6):1874-1886. [View Abstract]
- Salvilahti E. Food-induced malabsorption syndromes. J Pediatr Gastroenterol Nutr. 2000;30(Suppl):S61-S66. [View Abstract]
Codes
ICD09
ICD10
- K52.9 Noninfective gastroenteritis and colitis, unspecified
SNOMED
- 236071009 Chronic diarrhea (disorder)
- 15699003 Secretory diarrhea (disorder)
- 17551007 Chronic diarrhea of unknown origin (disorder)
- 25319005 Chronic diarrhea of infants AND/OR young children (disorder)
FAQ
- Q: If my infant has cow's milk allergy, when can he have cow's milk?
- A: In patients with cow's milk and/or soy allergy, rechallenge should be around 12 months of age and should be in a controlled environment in case anaphylaxis occurs. If the testing is negative, ingestion of cow's milk can be recommended.
- Q: What are the best markers for success in management of chronic diarrhea?
- A: If weight and height normalize, the chances of continued malabsorption are unlikely.