Approach
The diagnosis and differential diagnosis rely heavily on the patient’s history. Most cases of acute diarrhoea 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 centres do not have access to the rapid tests advocated by the ACG.
Diagnostic testing is indicated in severe diarrhoea (hypovolaemia, large volume/bloody diarrhoea, fever), persistent diarrhoea, and immunocompromised or older patients.[2][5]
History
In the vast majority of people, the diagnosis of acute diarrhoea 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 diarrhoea 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 diarrhoea and deciding on the need for further laboratory or endoscopic evaluation. Characteristics of the diarrhoea provide clues to the diagnosis. Specific points of the history include the following.
Onset of diarrhoea. Symptoms that begin within 6 hours of ingestion of contaminated food suggest a pre-formed toxin of Staphylococcus aureus or Bacillus cereus as the cause.
Frequency of stool passage. Diarrhoea due to infectious causes tends to have more frequent stool passage.
Amount of the stool. Toxin-induced diarrhoea tends to be large-volume (e.g., cholera) and osmotic diarrhoea smaller-volume.
Consistency of the stool. Watery diarrhoea tends to be associated with non-invasive 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 with recent types of food (meat, seafood, eggs, dairy) and water (well-water) ingestion, recent picnic, or barbecue 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 centres, 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 diarrhoea, but rarely helps to determine its cause. In most people, diarrhoea is a self-limiting disease, so physical examination may be entirely normal.
Important parameters that can help in assessing fluid balance include:
General appearance of the patient (i.e., whether unwell 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 dehydration)
Blood pressure
Orthostatic changes (e.g., symptomatic orthostatic hypotension).
Careful abdominal examination may reveal clues to some diagnoses. Patients may have hyperactive, normal, or absent bowel sounds, localised or generalised abdominal tenderness, rebound tenderness, abdominal distension, enlarged liver (in Salmonella, amoebic liver abscess), or an abdominal mass.
Rectal examination can help in characterising stool and content, presence of mucus, or blood and faecal 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 diarrhoea.[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 diarrhoea; 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 diarrhoea 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 diarrhoea with more than 4 stools per day and no vomiting pre-diarrhoea
Temperature >40°C (104°F)
Five or more stools in the previous 24 hours
Systemically unwell, severe or prolonged diarrhoea
History suggestive of food poisoning
Recent history of travel overseas
Stool tests
Stool for faecal leukocytes is one of the initial stool tests in suspected inflammatory diarrhoea. The sensitivity and specificity of faecal leukocytes for inflammatory diarrhoea are 73% and 84%, respectively.[68] False-negative and false-positive results are possible. The presence of faecal leukocytes and a positive occult blood test support the diagnosis of invasive or inflammatory diarrhoea such as inflammatory bowel disease.[69] Although the faecal leukocyte test is routinely recommended as an initial test for the evaluation of acute diarrhoea, it is rarely done in practice due to the suboptimal specificity.
Faecal lactoferrin assays were developed in response to the limitation of faecal leukocyte testing. Faecal lactoferrin sensitivity and specificity range from 90% to 100% in distinguishing inflammatory diarrhoea (bacterial colitis, inflammatory bowel disease) from non-inflammatory diarrhoea (irritable bowel syndrome).[70] Calprotectin is another marker of faecal 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 diarrhoea (bloody diarrhoea)
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 diarrhoea, but it can be useful in cases of persistent diarrhoea (14 to 30 days' duration). Specific indications to obtain stool for ova and parasites in patients with persistent diarrhoea include:
History - suggests infection with a specific parasite
Following travel to endemic or developing areas of the world
Exposure to infants in day care centres (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 diarrhoea with few or no faecal leukocytes (associated with intestinal amoebiasis)
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 neutralisation assay) directly in the stool. Molecular testing, the most common diagnostic method used, does not differentiate between infection and colonisation. It is highly sensitive with low/moderate specificity.[72] Stool cultures are the most sensitive test available, but are labour 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 diarrhoea (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 multi-step 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 diarrhoea, 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 diarrhoea. Faecal fat is also rarely helpful.
Blood tests
Diagnostic tests that may be considered in the diagnostic evaluation of acute diarrhoea in people with severe illness are:
FBC. This can help with assessing the severity of the diarrhoea (look for haemoconcentration, anaemia, and leukocytosis with left shift)
Serum chemistry. Electrolytes, urea nitrogen, and creatinine (look for hypokalaemia, acidosis, and renal dysfunction). Serum albumin and lactic acid (look for low albumin or raised lactic acid)
Antibody testing. May be considered for inflammatory bowel disease as an adjuvant to endoscopic and radiographic evaluation.
Radiological studies
Radiological studies are not needed in all patients. Studies including abdominal x-ray, or computed tomography scan of the abdomen and pelvis, are useful to identify some of the complications of acute diarrhoea, 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's disease.
Endoscopic evaluation
If all other tests are negative, endoscopic intervention (i.e., proctoscopy, flexible sigmoidoscopy, colonoscopy, oesophagogastroduodenoscopy, or video capsule endoscopy) will help in visualising 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 diarrhoea.
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 ischaemic colitis: findings vary and are non-specific; confirmation with a biopsy is required.
Asses for pathognomonic changes of ischemic colitis.
How to insert a peripheral venous cannula into the dorsum of the hand.
How to take a venous blood sample from the antecubital fossa using a vacuum needle.
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