Chronic Diarrhoea

Chronic diarrhoea is diarrhoea (loose or watery stools, with a stool weight above 200 g per day, or a stool frequency above 3 per day, or mushy or entirely liquid stool) lasting more than 4 weeks. It affects about 3 to 5% of adults, and has a major effect on quality of life.

• Categories (by mechanism and stool characteristics):
  • Osmotic: caused by poorly absorbed solutes (lactose, fructose, sorbitol, magnesium, polyethylene glycol, sugar alcohols). The diarrhoea stops with fasting, the stool osmotic gap is above 50 mOsm/kg, and the stool pH is below 6 in carbohydrate malabsorption.
  • Secretory: watery, large volume, persisting with fasting, with a stool osmotic gap below 50 mOsm/kg. Causes include bile acid diarrhoea, microscopic colitis, medicines, infection, neuroendocrine tumours (vasoactive intestinal peptide secreting tumours, carcinoid, gastrinoma, medullary thyroid carcinoma), laxative abuse, and villous adenoma.
  • Inflammatory: Crohn disease, ulcerative colitis, microscopic colitis, infections (Clostridioides difficile, tuberculosis, cytomegalovirus), ischaemic colitis, radiation colitis, diverticulitis, and colorectal cancer, with blood, mucus, pain, fever, raised faecal calprotectin.
  • Malabsorptive (fatty): coeliac disease, pancreatic exocrine insufficiency (chronic pancreatitis, cystic fibrosis, pancreatic cancer), small intestinal bacterial overgrowth, bile acid deficiency, short bowel syndrome, Whipple disease, giardiasis, and tropical sprue, with steatorrhoea, weight loss and nutrient deficiency.
  • Dysmotility: irritable bowel syndrome with diarrhoea, post-vagotomy, diabetic autonomic neuropathy, hyperthyroidism, and carcinoid.
  • Functional: irritable bowel syndrome with diarrhoea (the commonest cause in primary care, affecting about 5 to 10% of the population), and functional diarrhoea.
  • Medicines: metformin (up to 25%), magnesium containing antacids and laxatives, proton pump inhibitors, NSAIDs, colchicine, SSRIs, olmesartan, mycophenolate, antibiotics, chemotherapy, acarbose, orlistat, and sugar alcohols in sugar free products.
  • Others: lactose intolerance, fructose malabsorption, non-coeliac gluten sensitivity, HIV enteropathy, diabetes, thyrotoxicosis, Addison disease, amyloidosis, and faecal impaction with overflow.
• Prevalence of specific causes in primary care: irritable bowel syndrome (about 30 to 40% of those referred), bile acid diarrhoea (up to 25 to 30% of those thought to have irritable bowel syndrome with diarrhoea), microscopic colitis (about 10 to 15% of those with chronic watery diarrhoea, commoner in women over 50 years), coeliac disease (about 3 to 5% of those with chronic diarrhoea), and inflammatory bowel disease (up to 5 to 10%).

• Loose or watery stools for more than 4 weeks, with urgency, incontinence, abdominal cramps, bloating, flatulence, and nocturnal stools.
• Clues to the cause:
  • Weight loss, pale, bulky, floating, foul smelling stools that are difficult to flush (steatorrhoea), and nutrient deficiency (anaemia, osteoporosis, neuropathy, bruising): malabsorption (coeliac disease, pancreatic insufficiency).
  • Blood, mucus, abdominal pain, fever, extraintestinal features (arthritis, uveitis, skin lesions, mouth ulcers): inflammatory bowel disease.
  • Watery, often nocturnal diarrhoea with abdominal cramping in a middle aged woman, with autoimmune disease or NSAID, SSRI or proton pump inhibitor use: microscopic colitis.
  • Urgency and postprandial diarrhoea, after cholecystectomy or terminal ileal disease: bile acid diarrhoea.
  • Abdominal pain relieved by defecation, bloating, with alternating habit, and no alarm features: irritable bowel syndrome.
  • Bloating, flatulence and diarrhoea after dairy, fructose or fermentable sugars: carbohydrate intolerance.
  • Flushing, wheeze, palpitations: carcinoid. Tremor, heat intolerance, weight loss: hyperthyroidism. Diabetes with autonomic neuropathy: diabetic diarrhoea.
  • Epigastric pain, weight loss and steatorrhoea, with alcohol use: chronic pancreatitis.
  • Recent antibiotic exposure or travel: infections.
  • Frequent small stools with urgency, tenesmus and a sense of incomplete emptying in older adults: faecal impaction with overflow.
• Examination: weight and nutritional state, pallor, oedema, clubbing, oral ulcers, thyroid enlargement, abdominal tenderness, masses, hepatomegaly, skin lesions, and digital rectal examination for impaction, masses and sphincter tone.
• Differential diagnosis: irritable bowel syndrome with diarrhoea, bile acid diarrhoea, microscopic colitis, coeliac disease, inflammatory bowel disease, pancreatic exocrine insufficiency, small intestinal bacterial overgrowth, lactose and fructose malabsorption, medicine effects, thyrotoxicosis, faecal impaction with overflow, and colorectal cancer.
• Red flags: age over 50 years with new onset, rectal bleeding, unintentional weight loss, anaemia, nocturnal diarrhoea waking the patient, family history of colorectal cancer, inflammatory bowel disease or coeliac disease, abdominal mass, persistent fever, steatorrhoea, recent hospital stay or antibiotics, immunosuppression or HIV, and severe symptoms.
• Complications: dehydration, electrolyte disturbance (hypokalaemia, hypomagnesaemia, metabolic acidosis), malnutrition, anaemia, osteoporosis, faecal incontinence, perianal skin damage, and psychological distress.

• A structured approach: history (duration, frequency, volume, nocturnal symptoms, blood, steatorrhoea, diet, medicines, travel, family history, surgery, radiation, alcohol, HIV risk), examination including rectal examination, and a stool chart.
• First line tests in all patients:
  • Full blood count, ferritin, vitamin B12, folate, C-reactive protein, urea, electrolytes, creatinine, calcium, albumin, liver tests, glucose or HbA1c, and thyroid function tests.
  • Coeliac serology (tissue transglutaminase IgA with total IgA) while the patient is eating gluten.
  • Faecal calprotectin (below 50 micrograms/g makes inflammatory bowel disease unlikely, above 250 micrograms/g suggests it needs endoscopy, and 50 to 250 needs repeat testing and clinical correlation) or faecal lactoferrin.
  • Stool microscopy, culture, Giardia and Cryptosporidium antigen, ova and parasites, and Clostridioides difficile toxin when risk factors exist.
  • Faecal immunochemical test for blood, and HIV test when risk factors exist.
• Further investigations:
  • Faecal elastase (below 200 micrograms/g suggests pancreatic insufficiency, with values below 100 indicating severe insufficiency) and faecal fat estimation.
  • Colonoscopy with ileal intubation and biopsies from the right and left colon even when the mucosa looks normal (for microscopic colitis, Crohn disease, ulcerative colitis, and infection), for patients over 40 to 50 years, with red flags, raised calprotectin, or persistent unexplained diarrhoea.
  • Upper endoscopy with duodenal biopsies for coeliac disease (positive serology, or negative serology with high suspicion and IgA deficiency), and a small bowel aspirate or breath test for small intestinal bacterial overgrowth.
  • Bile acid diarrhoea: a bile acid retention scan (selenium labelled homotaurocholic acid), serum 7-alpha-hydroxy-4-cholesten-3-one (above 52.5 ng/mL suggests bile acid synthesis excess), or fasting fibroblast growth factor 19 (low), or a response to a bile acid binder.
  • Hydrogen breath tests for lactose, fructose and bacterial overgrowth.
  • Stool osmotic gap (290 minus 2 times the sum of stool sodium and potassium), stool pH, stool laxative screen for suspected factitious diarrhoea, and stool sodium.
  • Imaging: CT or MR enterography for small bowel disease, abdominal ultrasound, CT for pancreatic disease, and CT abdomen for suspected tumours.
  • Hormone tests (chromogranin A, urinary 5-hydroxyindoleacetic acid, vasoactive intestinal peptide, gastrin, calcitonin) for suspected neuroendocrine tumours.
  • Morning cortisol or short tetracosactide stimulation test (Addison disease), and nutritional assessment.
• A therapeutic test can be diagnostic: a lactose free diet for 2 to 4 weeks, a bile acid binder for 2 to 4 weeks, or a gluten free diet trial only after coeliac disease has been excluded (never before serology and biopsy in suspected coeliac disease).

• Treat the cause, and replace losses.
• Fluid and electrolyte replacement for dehydration and hypokalaemia (oral rehydration solution 200 to 400 mL after each loose stool, potassium chloride 600 to 1200 mg orally 8 to 12 hourly when low, and magnesium replacement), and nutritional support with dietitian review for weight loss and deficiency (iron, B12, folate, vitamin D, calcium, zinc, fat soluble vitamins).
• Review and stop medicines that cause diarrhoea (metformin (switch to extended release or reduce the dose), magnesium preparations, proton pump inhibitors, NSAIDs, colchicine, olmesartan, SSRIs, laxatives, sugar alcohols).
• Specific treatments:
  • Coeliac disease: strict lifelong gluten free diet, with dietitian support, correction of deficiencies, and screening for osteoporosis.
  • Microscopic colitis: budesonide 9 mg orally once daily for 8 weeks, then taper to 6 mg for 2 weeks and 3 mg for 2 weeks (or stop), with relapse in 60 to 80%, and maintenance with budesonide 3 to 6 mg daily for relapsing disease. Stop triggers (NSAIDs, proton pump inhibitors, SSRIs). Loperamide 2 to 4 mg 6 to 8 hourly or colestyramine 4 g orally once to 3 times daily are options for mild disease. Refer to a gastroenterologist for refractory disease (azathioprine, biologics).
  • Bile acid diarrhoea: colestyramine 4 g orally once daily, increased to 4 g up to 3 times daily (or colesevelam 625 mg to 1.875 g twice daily, or colestipol 5 g once daily to twice daily). Take other drugs at least 1 hour before, or 4 to 6 hours after, the bile acid binder. Adverse effects: bloating, constipation, nausea, and reduced absorption of fat soluble vitamins and drugs. Obeticholic acid and fibrate options are specialist led.
  • Irritable bowel syndrome with diarrhoea: dietary advice (regular meals, reducing caffeine, alcohol, fatty foods, and sorbitol), a low fermentable carbohydrate diet for 4 to 6 weeks with structured reintroduction, loperamide 2 mg once to 4 times daily (maximum 16 mg per day) as needed, amitriptyline 10 mg at night increased to 20 to 30 mg, peppermint oil 0.2 mL enteric coated capsule 3 times daily, rifaximin 550 mg orally 3 times daily for 14 days (for bloating and diarrhoea, retreating for relapse up to 2 times), and eluxadoline 100 mg orally twice daily with food (with careful selection) or ondansetron 4 mg once to 3 times daily in specialist care. Psychological therapies (cognitive behavioural therapy, gut directed hypnotherapy) help.
  • Inflammatory bowel disease: aminosalicylates, corticosteroids, immunomodulators and biologics under specialist care. Start mesalazine 2.4 to 4.8 g orally daily for mild to moderate ulcerative colitis, and prednisolone 40 mg daily with tapering for flares, in specialist care.
  • Pancreatic exocrine insufficiency: pancreatic enzyme replacement (lipase 40,000 to 50,000 units with each main meal and 20,000 to 25,000 units with snacks, titrated to a maximum of 10,000 units/kg per day), taken during meals, with a proton pump inhibitor if there is an inadequate response. Stop alcohol.
  • Small intestinal bacterial overgrowth: rifaximin 550 mg orally 3 times daily for 14 days (or 400 mg 3 times daily for 10 days), or ciprofloxacin 500 mg twice daily for 7 days, or amoxicillin clavulanate 625 mg 3 times daily for 7 days, with treatment of the cause (dysmotility, strictures, surgery) and repeat courses for relapse (most relapse within months).
  • Infection: giardiasis (tinidazole 2 g once, or metronidazole 400 mg 3 times daily for 5 days), Clostridioides difficile (fidaxomicin 200 mg twice daily for 10 days, or vancomycin 125 mg 4 times daily for 10 days), and others by culture.
  • Hyperthyroidism, Addison disease and diabetes: treat the cause.
  • Neuroendocrine tumours: octreotide 100 micrograms subcutaneously 8 hourly (or long acting 20 to 30 mg intramuscularly every 4 weeks) in specialist care.
  • Faecal impaction with overflow: disimpaction and a maintenance laxative regimen, not antimotility drugs.
  • Carbohydrate intolerance: lactose restriction or lactase supplementation, and a low fermentable carbohydrate diet for fructose.
  • Colorectal cancer: urgent surgical and oncology referral.
• Symptomatic therapy when the cause is unknown or while awaiting tests:
  • Loperamide 4 mg orally at first, then 2 mg after each loose stool, up to 16 mg per day, adjusted to stool consistency, and for chronic use at the lowest effective dose (2 mg once to twice daily). Avoid in inflammatory colitis flares and suspected infection.
  • Codeine phosphate 15 to 60 mg orally 6 to 8 hourly, as a second line option for short term use because of dependence.
  • Soluble fibre (ispaghula husk 3.5 g once to twice daily) to firm the stool.
• Special groups:
  • Children: chronic diarrhoea needs a growth assessment, coeliac serology, stool tests, and exclusion of cows' milk protein allergy, lactose intolerance, giardiasis and inflammatory bowel disease. Toddler's diarrhoea (normal growth, undigested food in loose stools, ages 1 to 5 years) needs reassurance, a normal fat intake, and reduced juice. Refer to paediatric gastroenterology for faltering growth, blood, or no clear cause.
  • Pregnancy: avoid colestyramine without monitoring of vitamin K, avoid fluoroquinolones and metronidazole in the first trimester, and manage infection and coeliac disease carefully. Loperamide is used for short courses.
  • Elderly: investigate for cancer, medicine effects, impaction and ischaemic colitis, and avoid opioids for long term use.
  • HIV: investigate for opportunistic infections (Cryptosporidium, microsporidia, cytomegalovirus, Mycobacterium avium complex), with antiretroviral therapy.
  • Renal impairment: monitor electrolytes, and avoid magnesium containing preparations.
• Follow up: review at 4 to 6 weeks after starting treatment, and arrange further tests for non-response. Refer urgently (within 2 weeks) for rectal bleeding, weight loss, anaemia, abdominal mass or age over 50 years with new symptoms. Refer to gastroenterology for unexplained persistent diarrhoea, abnormal calprotectin, malabsorption, or suspected inflammatory bowel disease.