Chronic diarrhoea (≥4 weeks) has an organic cause in ~30% of cases referred to secondary care — the challenge in primary care is identifying these. Colorectal cancer presenting with diarrhoea alone (without bleeding) is frequently right-sided and presents late — IDA may be the only clue. Nocturnal diarrhoea has >90% specificity for organic disease and should never be attributed to IBS. C. difficile is significantly under-recognised in primary care — rates of community-acquired C. diff have increased since 2010. In immunocompromised patients, any diarrhoea lasting >1 week requires specialist assessment due to the broad range of opportunistic pathogens.

Up to 25% of patients referred with "chronic diarrhoea" do not meet the objective definition — they have urgency, frequency of normal stools, or faecal incontinence, which require different management pathways. Drug-induced diarrhoea is underdiagnosed — metformin causes diarrhoea in up to 30% of patients and is often overlooked because it was started years before the symptom developed. Post-cholecystectomy bile acid malabsorption (BAM) affects 10% of patients and is frequently misdiagnosed as IBS — it responds to cholestyramine or colesevelam and can be confirmed with SeHCAT scan. Stool characteristics (fatty vs watery vs bloody) point to completely different pathophysiological mechanisms and diagnostic pathways.

Mechanistic classification directs investigation efficiently. Osmotic diarrhoea that stops with fasting does not need colonoscopy — dietary exclusion and coeliac screen are the first steps. Secretory diarrhoea that persists with fasting requires endoscopic investigation (microscopic colitis is invisible to the naked eye — biopsies are mandatory). Malabsorptive diarrhoea needs coeliac serology and faecal elastase (for pancreatic exocrine insufficiency) before colonoscopy. IBS-D is a clinical diagnosis requiring Rome IV criteria AND normal investigations — it must not be diagnosed by exclusion alone without appropriate workup, particularly in patients over 50.

Dermatitis herpetiformis is pathognomonic for coeliac disease — if you see this on skin, the diagnosis is made. Up to 25% of Crohn's disease patients have perianal involvement (fistulae, abscesses, fissures, skin tags) — finding this on PR exam should dramatically raise suspicion for Crohn's and expedite referral. PSC (primary sclerosing cholangitis) occurs in 5% of UC patients and can present before bowel symptoms — abnormal LFTs with IBD should always trigger PSC investigation (ALP elevated, MRCP). Hypoalbuminaemia (<30 g/L) with diarrhoea indicates severe malabsorption or protein-losing enteropathy and requires urgent secondary care assessment.

Faecal calprotectin is endorsed by NICE (DG11) for distinguishing IBD from IBS in adults with diarrhoea. NPV of 97% for IBD when <50 µg/g — this is one of the most powerful negative predictive tests in gastroenterology and allows safe avoidance of colonoscopy in the majority of patients. Sensitivity for IBD at >200 µg/g is 93%. Coeliac disease affects 1% of the UK population — anti-tTG IgA has 93% sensitivity but will be falsely negative in 2–3% due to IgA deficiency (always check total IgA). The patient must be eating gluten (≥2 slices bread/day for ≥6 weeks) for the test to be valid. Microscopic colitis is the most underdiagnosed cause of chronic watery diarrhoea in women over 50 — it is invisible at colonoscopy and requires colonic biopsies specifically; calprotectin may be only mildly elevated.

Toxic megacolon (UC complication — transverse colon >6cm on AXR) carries 20–30% mortality without emergency colectomy — it must be identified and referred within hours. Severe UC (Truelove & Witts criteria: ≥6 bloody stools/day + systemic upset) has a 30-day mortality of ~2% even with treatment — these patients need IV steroids in hospital, not oral treatment at home. Carcinoid tumours and VIPomas are rare but important: diarrhoea + flushing + tachycardia → check 5-HIAA in urine (carcinoid) or VIP levels (VIPoma) — both require oncology input. Positive coeliac serology should always be referred for biopsy before starting gluten-free diet — biopsy is the gold standard and becomes negative (falsely normal) on a gluten-free diet.

Colesevelam is preferred over cholestyramine for bile acid malabsorption — better tolerability (tablet vs powder), fewer drug interactions, similar efficacy. BAM responds to bile acid sequestrants in 70% of cases. Creon (PERT) for pancreatic exocrine insufficiency: PPI co-prescription is mandatory — gastric acid inactivates lipase, reducing PERT efficacy by up to 40%. Budesonide for microscopic colitis has 80% remission rate (Cochrane 2016) — it is the only NICE-endorsed treatment and significantly superior to mesalazine or bismuth. Critically, loperamide is contraindicated in severe IBD flares (Truelove & Witts severe) and C. difficile — it can precipitate toxic megacolon by reducing gut motility and allowing toxin accumulation.

Low-FODMAP diet has the strongest dietary evidence for IBS-D — multiple RCTs showing 75% symptom response rate, superior to a standard healthy eating diet. It requires dietitian supervision because unsupervised restriction leads to nutritional deficiencies and an overly restrictive diet long-term. CBT for IBS has NNT of 3–4 for significant improvement — it should be offered to all patients who do not respond to initial pharmacological treatment. Metformin modified-release formulation reduces GI side effects by ~50% compared with immediate-release — this simple switch is under-utilised and can be done in primary care without specialist input. Probiotics for IBS: BSG 2021 guidelines recommend a trial of a multi-strain probiotic for at least 4 weeks as they are safe and have moderate evidence of benefit.

Coeliac disease annual monitoring is mandatory — untreated or poorly adherent coeliac disease increases risk of enteropathy-associated T-cell lymphoma (EATL, rare but serious), osteoporosis, and nutritional deficiencies. Anti-tTG IgA should normalise within 12 months of strict GFD — failure to normalise indicates ongoing gluten exposure (intentional or inadvertent). C. difficile recurrence monitoring is critical — 25% of patients recur and each recurrence increases the risk of subsequent recurrences. NICE endorses fidaxomicin for recurrent C. diff (TA). FMT achieves 90% success rate for multiply-recurrent C. diff. In patients over 50 with previously "diagnosed" IBS, any change in symptom pattern should trigger re-investigation — new colorectal cancer developing in patients with IBS is a documented pattern of delayed diagnosis.