Approach
The diagnosis and differential diagnosis rely heavily on the patient’s history. Most cases of acute diarrhea are self-limiting, and further evaluation is not needed. However, the American College of Gastroenterologists (ACG) highlights that this approach may be a barrier to providing appropriate directed therapies that can result in more rapid symptom resolution and potentially prevent postinfectious complications.[2] On a practical level, many centers do not have access to the rapid tests advocated by the ACG.
Diagnostic testing is indicated in severe diarrhea (hypovolemia, large volume/bloody diarrhea, fever), persistent diarrhea, and immunocompromised or older patients.[2][5]
History
In the vast majority of people, the diagnosis of acute diarrhea is made exclusively by history and physical examination because it is impractical to collect and weigh the stool expelled over 24 hours. A clinically pertinent definition of diarrhea is passage of three or more loose or liquid stools per 24 hours, or more frequently than what is normal for the individual. A full history and physical examination are very helpful in contemplating the specific cause of diarrhea and deciding on the need for further laboratory or endoscopic evaluation. Characteristics of the diarrhea provide clues to the diagnosis. Specific points of the history include the following.
Onset of diarrhea. Symptoms that begin within 6 hours of ingestion of contaminated food suggest a preformed toxin of Staphylococcus aureus or Bacillus cereus as the cause.
Frequency of stool passage. Diarrhea due to infectious causes tends to have more frequent stool passage.
Amount of the stool. Toxin-induced diarrhea tends to be large-volume (e.g., cholera) and osmotic diarrhea smaller-volume.
Consistency of the stool. Watery diarrhea tends to be associated with noninvasive and toxin-producing pathogens.
Blood in the stool. Suggests invasive pathogens or severe inflammation (e.g., ulcerative colitis).
Mucus or pus in the stool. Seen usually in colonic involvement with inflammatory processes or infective pathogens.
Fever. If present, suggests infection with invasive bacteria (e.g., Salmonella, Shigella, or Campylobacter), enteric viruses, or a cytotoxic organism such as Clostridioides difficile or Entamoeba histolytica.
Recent travel. A history of travel to endemic regions may point to a specific pathogen. Infection with Giardia, Cryptosporidium, and Cyclospora can occur in Russia, Nepal, eastern Europe, or mountainous regions.
Dietary history. Recent types of food (meat, seafood, eggs, dairy) and water (well-water) ingestion, recent picnic, or cookouts may all be suggestive of infectious causes (e.g., Campylobacter, Salmonella, Shigella, Escherichia coli, or C difficile).
Exposure to pets or cattle.
Associated symptoms. Abdominal pain (e.g., invasive organisms), nausea (e.g., Cryptosporidium), vomiting (e.g., preformed toxins), bloating, flatus (e.g., Giardia), fever, tenesmus (left-sided colitis), anal itch.
Drugs, specifically recent use of antibiotics or laxatives.
Past medical or surgical history.
Social history. Sexual practice, drug use, alcohol use.
Occupational history. Workers in day care centers, hospitals, mental institutions, and nursing homes may be exposed to Giardia, Cryptosporidium, and norovirus.
Physical examination
Physical examination is used to assess the severity of the diarrhea but rarely helps to determine its cause. In most people, diarrhea is a self-limiting disease, so physical examination may be entirely normal.
Important parameters that can help in evaluating fluid balance include:
General appearance of the patient (i.e., whether ill or well, and nutritional status)
Pulse
Skin turgor
Whether or not mucous membranes appear dry
Capillary refill time (usually <3 seconds, but may be increased in volume depletion)
Blood pressure
Orthostatic changes (such as symptomatic orthostatic hypotension).
Careful abdominal examination may reveal clues to some diagnoses. Patients may have hyperactive, normal, or absent bowel sounds, localized or generalized abdominal tenderness, rebound tenderness, abdominal distention, enlarged liver (in Salmonella, amebic liver abscess), or an abdominal mass.
Rectal examination can help in characterizing stool and content, presence of mucus or blood, and fecal occult blood testing.
Indications for diagnostic testing
A close, positive working relationship between the physician and the microbiologist is needed to determine the best use of laboratory testing in cases of acute diarrhea.[66] According to the American College of Gastroenterology, diagnostic evaluation is indicated in patients with relatively severe illness, as suggested by one or more of the following:[2]
Dysentery
Moderate-to-severe disease (severe = total disability due to diarrhea; moderate = able to function but with forced change in activities)
Symptoms lasting >7 days
At high risk for spreading disease to others
According to guidelines for the management of diarrhea in children with or without vomiting, diagnostic testing is indicated by one or more of the following:[67]
History of blood with or without mucus in the stool
Combination of abrupt onset of diarrhea with more than 4 stools per day and no vomiting pre-diarrhea
Temperature >104°F (40°C)
Five or more stools in the previous 24 hours
Systemically ill, severe or prolonged diarrhea
History suggestive of food poisoning
Recent history of travel overseas
Stool tests
Stool for fecal leukocytes is one of the initial stool tests in suspected inflammatory diarrhea. The sensitivity and specificity of fecal leukocytes for inflammatory diarrhea are 73% and 84%, respectively.[68] False-negative and false-positive results are possible. The presence of fecal leukocytes and a positive occult blood test support the diagnosis of invasive or inflammatory diarrhea such as inflammatory bowel disease.[69] Although the fecal leukocyte test is routinely recommended as an initial test for the evaluation of acute diarrhea, it is rarely done in practice due to the suboptimal specificity.
Fecal lactoferrin assays were developed in response to the limitation of fecal leukocyte testing. Fecal lactoferrin sensitivity and specificity range from 90% to 100% in distinguishing inflammatory diarrhea (bacterial colitis, inflammatory bowel disease) from noninflammatory diarrhea (irritable bowel syndrome).[70] Calprotectin is another marker of fecal inflammation and can differentiate inflammatory bowel disease from functional disorders.[70][71]
Stool culture, which most often tests for E coli, Campylobacter, Shigella, Salmonella, and Yersinia, (if specifically requested), is usually done in the following circumstances:[66]
Immunocompromised patients, including those infected with HIV
Patients with multiple comorbidities
Patients with severe inflammatory diarrhea (bloody diarrhea)
Patients with underlying inflammatory bowel disease in whom the distinction between a flare and superimposed infection is critical
The test for stool leukocytes is positive
Some employees, such as food handlers, who occasionally require negative stool cultures to return to work
Outbreak investigations
Stool for ova and parasites is rarely helpful early in the evaluation of acute diarrhea, but it can be useful in cases of persistent diarrhea (14 to 30 days' duration). Specific indications to obtain stool for ova and parasites in patients with persistent diarrhea include:
History - suggests infection with a specific parasite
Following travel to endemic or developing areas of the world
Exposure to infants in day care centers (associated with Giardia and Cryptosporidium)
Men who have sex with men or a patient with AIDS (associated with Giardia, Cryptosporidium, and Entamoeba histolytica and a variety of other parasites)
A community waterborne outbreak (associated with Giardia and Cryptosporidium)
Bloody diarrhea with few or no fecal leukocytes (associated with intestinal amebiasis)
Stool Giardia and Cryptosporidium antigen testing has a higher sensitivity than stool ova and parasites and should be requested if either is suspected from the history.
Tests for C difficile detect either the organism itself (i.e., nucleic acid amplification tests [NAAT], such as stool polymerase chain reaction (PCR), glutamate dehydrogenase [GDH] enzyme immunoassay, or toxigenic culture) or its major toxins (i.e., toxin A and B enzyme immunoassays, cell culture cytotoxicity neutralization assay) directly in the stool. Molecular testing, the most common diagnostic method used, does not differentiate between infection and colonization. It is highly sensitive with low/moderate specificity.[72] Stool cultures are the most sensitive test available, but are labor intensive, require an appropriate culture environment, and take 48 to 96 hours for results. They are not typically used in practice.[73]
In the interests of good diagnostic stewardship, it is recommended that C difficile testing is limited to patients with unexplained, new-onset diarrhea (defined as 3 or more unformed stools in 24 hours) who are not receiving laxatives in the last 48 hours; however, this recommendation is based on very low-quality evidence.[72]
If hospital and laboratory personnel agree on this stool submission criteria, NAAT alone is recommended as this is the most sensitive method of diagnosis in stool specimens from patients who are likely to have C difficile infection based on clinical symptoms.
However, if there are no pre-agreed institutional criteria for patient stool submission, a stool toxin test as part of a multistep algorithm is recommended (e.g., GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than NAAT alone.
Repeat testing should not be performed within 7 days during the same episode of diarrhea, and asymptomatic patients should not be tested.
European guidelines for C difficile testing recommend a two-step algorithm, starting with a highly sensitive test (e.g., NAAT, or GDH enzyme immunoassay) and, if positive, confirmation with a highly specific test (toxin A/B enzyme immunoassay). Alternatively, samples can be screened with both a GDH and toxin A/B enzyme immunoassay.[74]
Multiplex PCR tests have been developed and used to yield quicker and broader identification of viral, bacterial, and protozoal pathogens. These technological advances are frequently used now, although they are still unavailable in some settings despite their ability to diagnose gastrointestinal (GI) infections more rapidly and sensitively than other tests. While multiplex PCR tests increase the diagnostic yield, there are some drawbacks; the significance of detected organisms that these tests detect is not always clear with, for example, asymptomatic carriage of potential pathogens, multi-organism identification, and their inability to discriminate between viable and non-viable organisms. In addition, microscopy is still necessary for identification of some helminth and intestinal protozoa in tropical settings.[75] These culture and microscopy-independent diagnostic tests are recommended as an adjunct to the more traditional diagnostic methods.[2] Additionally, there are limited data available on the cost effectiveness of the use of GI multiplex panels as the only diagnostic tool.
Laxative screen can be performed when laxative use or misuse is suspected.
Stool weight, electrolytes, and osmotic gap are rarely if ever done in the evaluation of acute diarrhea. Fecal fat is also rarely helpful.
Blood tests
Diagnostic tests that may be considered in the diagnostic evaluation of acute diarrhea in people with severe illness are:
CBC. This can help with assessing the severity of the diarrhea (look for hemoconcentration, anemia, and leukocytosis with left shift)
Serum chemistry. Electrolytes, BUN, and creatinine (look for hypokalemia, acidosis, and renal dysfunction). Serum albumin and lactic acid (look for low albumin or elevated lactic acid)
Antibody testing. May be considered for inflammatory bowel disease as an adjuvant to endoscopic and radiographic evaluation.
Radiologic studies
Radiologic studies are not needed in all patients. Studies including abdominal radiograph or computed tomography scan of the abdomen and pelvis are useful to identify some of the complications of acute diarrhea, such as ileus, perforation, or megacolon.
Toxic megacolon or perforation may be found in patients with C difficile or Yersinia infection, ulcerative colitis, and Crohn disease.
Endoscopic evaluation
If all other tests are negative, endoscopic intervention (i.e., proctoscopy, flexible sigmoidoscopy, colonoscopy, esophagogastroduodenoscopy, or video capsule endoscopy) will help in visualizing the GI tract and obtaining biopsy (for histology and culture) as well as fluids for analysis and culture. Colonoscopy rather than sigmoidoscopy should be used in immunocompromised patients.[76] Endoscopy can be considered to:
Distinguish inflammatory bowel disease from infectious diarrhea.
Rapidly diagnose C difficile infection by the presence of a pseudomembrane; the widespread use of enzyme-linked immunosorbent assay for C difficile toxins A and B, and PCR, has reduced the time for C difficile results to become available and therefore decreased the need for endoscopic evaluation.
Evaluate for opportunistic infections such as cytomegalovirus and herpes simplex virus infection, as well as graft-versus-host disease in immunocompromised patients, and ischemic colitis: findings vary and are nonspecific; confirmation with a biopsy is required.
Asses for pathognomonic changes of ischemic colitis.
How to insert a peripheral intravascular catheter into the dorsum of the hand.
How to take a venous blood sample from the antecubital fossa using a vacuum needle.
Use of this content is subject to our disclaimer