Investigating diarrhoea – a rational approach to testing in primary care

Gastroenterology specialists Dr Andy Li and Dr Jessica Gurung outline logical steps for laboratory testing in a case of recurrent diarrhoea in a young adult woman

A 21-year-old female patient attends complaining of recurrent diarrhoea. She has suffered this for a few years but the symptoms have got worse recently since she has been under stress at work. When suffering a ‘flare’ she has to open her bowels five or six times per day, especially in the morning, often with a sense of urgency. She gets colicky pain, too, relieved by defaecation, and often feels bloated. There is no rectal bleeding and her weight is steady. She is a non-smoker, drinks very little and is on no medication. Dietary exclusions haven’t helped at all. Her mother has IBS and having Googled it, she thinks this is likely to be her diagnosis. ‘I’d like to be tested for this,’ she says.

What would be the ‘bare minimum’ set of lab tests in this situation?

This is a common clinical scenario that is encountered by both GPs and gastroenterology. Based on the information so far, the most likely diagnosis is Irritable Bowel Syndrome (IBS). IBS is a clinical diagnosis, using the Rome IV criteria, and not one of exclusion:¹

Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months (with symptom onset at least 6 months prior to diagnosis) which is associated with two or more or the following:

Related to defaecation;
Change in frequency of stool;
Change in stool form.

While it’s tempting to offer a barrage of tests, the diagnostic yield and relevance of each of these must be considered. Blanket testing leads to diagnostic delay, equivocal results and unnecessary secondary care referrals. Further investigations by way of biochemical or stool testing should only be performed if there is suspicion of underlying organic disease or uncertainty.

While NICE guidelines recommend a select few tests in suspected IBS (full blood count, C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and coeliac serology) the table below offers a slightly extended panel that screens for other common causes of chronic diarrhoea.

Table 1: Key basic first line tests for investigating chronic diarrhoea

Blood and other tests	Clinical significance
Ful blood count, iron studies, vitamin B12 and folate	To screen for anaemia and/or vitamin deficiencies suggestive of malignancy or malabsorption
ESR/CRP	To assess for activity/severity of inflammation.
IgA anti-tTG or IgA anti-endomysial antibody (EMA)	Coeliac serology is only reliable if consuming gluten at time of testing. Gluten-free diet will likely produce a falsely negative result. A gluten challenge should be proposed if clinical suspicion is high with retesting in 6-8 weeks’ time.
Thyroid function	Hyperthyroidism, particularly useful in scenarios of chronic unexplained diarrhoea.
Faecal calprotectin (FCP)	Can be utilised as a first line test to help distinguish between functional causes of diarrhoea versus true inflammatory bowel disease (IBD).² FCP is a non-specific marker of gut inflammation. It is a protein that is found in high concentrations within neutrophils. FCP can be elevated in infection, inflammation and colorectal cancer.³ A raised FCP sampled in acute infectious diarrhoea does notnecessarily indicate IBD, so should be interpreted with this in mind. It can be repeated a few weeks later if there is diagnostic uncertainty.

Pertinent questioning regarding abdominal surgeries such as cholecystectomy, travel, antibiotic usage, recent systemic illness and family history can rapidly identify individuals at high risk of true pathology. Screening for extraintestinal features of inflammatory bowel disease (IBD), such as uveitis, aphthous ulcers, arthralgia and erythema nodosum/pyoderma gangrenosum is good practice and easily forgotten but these can occur in up to 50% of IBD patients.⁴

Stress is a common trigger for functional gut disease, and exploration of environment can reveal hidden causes of diarrhoea including laxative abuse, dieting and excess alcohol consumption.

Clinical examination is often completely normal, but on the rare occasion may pick up a subtle sign suggestive of further disease. For example, proptosis or goitre in hyperthyroidism and dermatitis herpetiformis in coeliac disease. A rectal exam may be warranted if the history is suggestive of bleeding or rectal pain.

What might be add-on tests and when might you consider them?

Any atypical features or suspicious history should prompt further thought. The table below outlines key adjuncts to the prior investigations.

Table 2. Additional tests for investigating chronic diarrhoea in primary care

Investigation	Clinical cue	Additional notes
Renal function	Useful if diarrhoea is prolonged	To assess for electrolyte abnormality
Bone profile (including calcium, phosphate)	Can be indirect marker of underlying malignancy (hypercalcemia) or malabsorption	Hypocalcaemia and hypophosphatemia in coeliac disease or IBD.
Stool microscopy, culture and sensitivity (MCS) and Clostridium difficile toxin/antigen	Acute infectious history. Risk factors for C difficile include elderly, hospitalisation, antibiotic use or immunocompromised individuals.	Stool MCS screens for a profile of common bacteria – Campylobacter, Salmonella, E coli and Yersinia.
Stool ova and parasites	Travel history, including both domestic and international. Note freshwater sources, such as lakes, rivers and even wells are recognised reservoirs for Giardia, with outdoor pursuits (e.g. camping, hiking, wild swimming) posing an increased risk of consuming untreated water.	Giardiasis is the commonest protozoal cause, particularly following travel to South Asia, and should be considered if diarrhoea is prolonged and bacterial causes have been excluded.⁵ Three stool samples should be taken, each two days apart (as this is the time taken to shed ova).
HIV serology	Screen in high-risk populations. Risky behaviours – e.g. multiple sexual partners, intravenous drug users.	HIV associated enteropathy can cause acute or chronic diarrhoea in the context of systemic features – e.g. weight loss.

The urgent suspected cancer pathway for colorectal cancer prompts secondary care referrals and investigations.⁶Unexplained weight loss, rectal bleeding, abdominal pain, change in bowel habits, weight loss and iron deficiency anaemia should raise alarm in patients aged 40 years and above. Inevitably, there will be individuals that fall below the threshold for this pathway but do require further investigation. A faecal immunochemical test (FIT) in these situations can help stratify need for subsequent tests.

What tests are often done in this scenario but not appropriate and to be avoided?

Cross-sectional imaging should be reserved for a select cohort of patients that raise suspicion of small bowel related pathology which would not be amenable to colonoscopy. FIT testing in the young, otherwise well individual with no clinical concern for cancer or rectal bleeding is an unnecessary, low-value test. Similarly, FCP collected during an acute infectious diarrhoea is inevitably elevated. These can spiral into unwarranted colonoscopies, which should be considered carefully as this is not devoid of procedural risk. Simply repeating the stool sample in a few weeks’ time post episode can provide reassurance of transient gut inflammation. Lastly, faecal elastase should only be tested for if genuine concern for malabsorptive diarrhoea with risk factors such as alcohol excess and previous acute pancreatitis episodes.

Dr Andy Li is consultant gastroenterologist and Dr Jessica Gurung is specialist registrar in gastroenterology at University Hospitals Sussex NHS Foundation Trust