Differential Diagnosis of Chronic Diarrhoea
The differential diagnosis of chronic diarrhoea in adults with no significant past medical history should be systematically categorized into watery (osmotic, secretory, functional), fatty (malabsorptive), and inflammatory types, with irritable bowel syndrome being the most common cause overall, but organic diseases such as coeliac disease, microscopic colitis, inflammatory bowel disease, and bile acid diarrhoea requiring exclusion through targeted investigation. 1, 2
Categorization by Diarrhoea Type
The most practical diagnostic approach is to categorize diarrhoea by pathophysiologic mechanism, which narrows the differential diagnosis and guides targeted testing 1, 2:
Watery Diarrhoea
Functional causes:
- Irritable bowel syndrome with diarrhoea (IBS-D) is the most common cause of chronic functional diarrhoea, characterized by abdominal pain that peaks before defecation, is relieved by defecation, and is associated with changes in stool form or frequency 3, 2
- Functional diarrhoea differs from IBS-D in that abdominal pain is not a primary diagnostic criterion 4
Secretory causes:
- Microscopic colitis accounts for 15% of chronic diarrhoea cases in older adults and has entirely normal-appearing mucosa on endoscopy but shows characteristic histologic changes only on biopsy 5, 2
- Bile acid malabsorption should be considered when colonoscopy is negative 5, 1
- Endocrine disorders including hyperthyroidism 6, 1
- Post-surgical states including vagal nerve damage, gastric resection, or gut bypass reducing absorptive capacity 7, 1
Osmotic causes:
Fatty Diarrhoea (Malabsorptive/Maldigestive)
Small bowel causes:
- Coeliac disease is the most common small bowel enteropathy in Western populations and typically results in weight loss and iron deficiency anaemia 7, 6, 1, 2
- Small bowel bacterial overgrowth (SBBO) is more likely in patients with anatomical abnormalities such as dilation, diverticulosis, prior small bowel surgery, or pseudo-obstruction 7, 6
- Giardiasis is a classic infectious malabsorptive cause 6, 2
Pancreatic causes:
Inflammatory Diarrhoea
Inflammatory bowel disease:
- Crohn's disease or ulcerative colitis characterized by blood and pus in stool and elevated fecal calprotectin 5, 1, 2
Infections:
- Clostridioides difficile colitis particularly if recent antibiotic exposure 5, 1, 2
- Invasive bacteria and parasites 2
Neoplasia:
Critical Red Flag Features Indicating Organic Disease
Alarm features that mandate urgent investigation include:
- Nocturnal diarrhoea strongly indicates organic pathology rather than functional disorders and warrants expedited evaluation 9, 6, 5
- Recent worsening of chronic symptoms suggests progressive organic disease requiring immediate evaluation 9, 5
- Fecal incontinence during sleep indicates severe disease burden 5
- Blood in stool 1, 2
- Unintentional weight loss 1, 2
- Iron deficiency anaemia 7, 9, 2
Surgical and Structural Causes
Post-surgical diarrhoea may be attributed to pyloric dysfunction, bile salt malabsorption, bacterial overgrowth, or gut bypass reducing absorptive capacity 7
Faecal incontinence may be the primary presenting symptom with underlying diarrhoea as the causative factor, particularly in patients with compromised sphincter complex from obstetric trauma, pelvic surgery, obesity, diabetes, or stroke 7
Overflow diarrhoea from severe faecal loading occurs in patients with cognitive or behavioural issues, learning difficulties, or neurological/spinal disease 7
Common Pitfalls to Avoid
Do not diagnose IBS in patients with nocturnal diarrhoea, as this is an exclusion criterion for functional disorders 6, 5
Do not skip colonic biopsies even with normal-appearing mucosa, as microscopic colitis requires histologic diagnosis 6, 5
Unrecognised cases of coeliac disease are sometimes falsely diagnosed as diarrhoea-predominant IBS in colorectal clinics 7
Do not rely on CT imaging alone, as it is inadequate for detecting microscopic colitis, early inflammatory bowel disease, or subtle mucosal abnormalities 5