Editors

KalleJokelainen

Prolonged Diarrhoea in Adults

Essentials

An estimated 4-5% of adults in western countries have prolonged diarrhoea.
Prolonged diarrhoea affects the quality of life significantly. Chronic diarrhoea is one of the most common reasons for seeing a doctor.
Prolonged diarrhoea may represent a completely benign functional problem or be due to a disease that may prove fatal if left untreated.
Prolonged diarrhoea may be caused by inflammatory conditions, tumours, malabsorption, infections, food intolerance, functional problems, several medications, post-operative sequelae, endocrine diseases (diabetes, hyperthyroidism) or chronic mesenteric ischaemia, for example.
Food, any recent travel abroad, medication and previous abdominal surgical procedures or radiotherapy as possible causes of diarrhoea should be considered first.
Prolonged diarrhoea is rarely caused by an infection unless the patient is immunocompromised. Possible causative agents include Giardia lamblia Giardiasis, Clostridioides difficile Clostridioides Difficile Diarrhoea and Entamoeba histolytica Amoebiasis.
It is important to identify irritable bowel syndrome (IBS Functional Bowel Disorders and the Irritable Bowel Syndrome (IBS)) because some IBS patients, at least, have diarrhoea. IBS symptoms may also appear after infectious gastroenteritis.
Faecal impaction may cause so-called overflow diarrhoea especially in elderly persons in institutional care whose level of physical activity is often low and who are taking medication reducing intestinal motility.
It is important to distinguish between true prolonged diarrhoea and faecal incontinence.
The most common malabsorption disorders (coeliac disease Coeliac Disease, lactose intolerance Lactose Intolerance) should be detected and patients should be referred for colonoscopy Colonoscopy and Sigmoidoscopy to diagnose inflammatory bowel diseases (ulcerative colitis Ulcerative Colitis, Crohn's disease Crohn's Disease, microscopic colitis Microscopic Colitis), as recommended and necessary.

Definition

Criteria for prolonged diarrhoea:
- more than 3 defecations daily and/or loose faecal consistency (watery stools); amount of faeces more than 200 g/24 hours
- duration of diarrhoea exceeding 4 weeks.
The normal frequency of bowel movements may vary from 3 times daily to 3 times weekly.

Aetiology

Prolonged diarrhoea is usually divided into three main types: watery, fatty and inflammatory (Table T1).
Prolonged diarrhoea usually represents a combination of various types of diarrhoea, where one component may be dominant.
Investigations should be planned based on other symptoms associated with the diarrhoea.
- Abdominal pain, fever and bloody diarrhoea may be due to chronic inflammatory bowel disease.
- Weight loss may be due to malabsorption or a malignancy.
- Nocturnal sweating may be a symptom of lymphoma.
- Anaemia and a changed calibre of faeces may be due to colorectal cancer.
Intestinal causes
- Irritable bowel syndrome (IBS) Functional Bowel Disorders and the Irritable Bowel Syndrome (IBS) is the most common cause of recurrent diarrhoea. Diagnosis is based on the clinical picture and on exclusion of organic diseases. The extent of examinations to rule out possible causes is determined individually. Infectious gastroenteritis may cause diarrhoea-predominant IBS in 2-10% of patients, and in 50% of these the IBS still continues 2 years after the acute infection.
- Colitis: ulcerative colitis Ulcerative Colitis (bloody diarrhoea), Crohn's disease Crohn's Disease, microscopic colitis Microscopic Colitis (collagen colitis and lymphocytic colitis)
- Coeliac disease Coeliac Disease
- Malignancies: cancer of the large intestine or rectum Colorectal Cancer and other gastrointestinal malignancies
- Surgical procedures (vagotomy, gastrectomy, fundoplication, bariatric surgery, cholecystectomy, ileocolic bowel resection)
Systemic diseases
- Hyperthyroidism, HIV infection, diabetic autonomic neuropathy, uraemia, hypoparathyroidism, Addison's disease, hormone secreting tumour (carcinoid, gastrinoma, VIPoma)
- Chronic pancreatitis Chronic Pancreatitis, pancreatic cancer Carcinoma of the Pancreas, cystic fibrosis Cystic Fibrosis (CF)
- Bile acid malabsorption
  - Bile acid diarrhoea may result from a disease of the distal small intestine (Crohn's disease, radiation injury) or ileal resection. It may also be idiopathic without structural abnormality of the ileum.
  - 25-50% of patients suffering from functional diarrhoea or diarrhoea-predominant IBS may have bile acid diarrhoea.
Dietary factors
- Lactose malabsorption Lactose Intolerance is common, and it may be an insignificant incidental finding. Hypolactasia may be secondary to coeliac disease or occur in the convalescent phase of severe gastroenteritis.
- Xylitol, sorbitol, and fructose are poorly absorbed and may cause diarrhoea. Carbohydrate malabsorption often involves abdominal swelling and flatulence.
- Wheat, rye and barley cause symptoms in patients with coeliac disease Coeliac Disease.
- Excessive consumption of alcohol may cause diarrhoea.
- Food allergy is rare in adults. Latex-fruit/vegetable allergy may cause diarrhoea.
Drugs
- Laxatives, antimicrobial drugs, magnesium-containing antacids, iron, metformin, NSAIDs, cytotoxic drugs, acid blockers (PPIs, H2 blockers), gliptins, natural products and vitamins and trace elements (vitamin C, magnesium) are the most common causes of diarrhoea.
- Laxative abuse or addition of water/urine to faeces will cause factitious diarrhoea. Laxatives or their metabolites can be determined in serum samples if abuse is suspected. An increased faecal magnesium concentration suggests (ab)use of antacids containing magnesium.
- Antimicrobials may cause Clostridioides difficile diarrhoea Clostridioides Difficile Diarrhoea (pseudomembranous colitis).
Prolonged diarrhoea is rarely caused by microbes unless the patient has immunodeficiency or is on immunosuppressive medication. For diagnosis, see Diarrhoeal Diseases Caused by Microbes.
- Parasitic infection is the most common microbial aetiology of prolonged diarrhoea (Entamoeba histolytica Amoebiasis, Giardia lamblia Giardiasis, Dientamoeba fragilis Dientamoebiasis in Adults, Cryptosporidium Cryptosporidiosis, Cyclospora cayatensisCryptosporidiosis, Cystoisospora belli Cryptosporidiosis, Microsporidia, Blastocystis hominis).
  - Diarrhoea caused by giardiasis Giardiasis typically has a subacute onset, i.e. only begins after returning from travel.
- Intestinal worms may also cause prolonged diarrhoea: the nematode Strongyloides Strongyloidiasis, roundworm Ascaris lumbricoides Ascariasis, hookworms Ancylostoma duodenale or Necator americanus Hookworm Disease, whipworm Trichuris trichiura Trichuriasis, broad tapeworms Diphyllobothrium latum and D. nihonkaiense Tapeworm Disease.
- The following bacteria may cause chronic diarrhoea: Yersinia enterocoliticaYersiniosis, Aeromonas hydrophila, Plesiomonas shigelloides, Clostridioides difficileClostridioides Difficile Diarrhoea, Mycobacterium tuberculosisDiagnosing Tuberculosis and Tropheryma whipplei (Whipple's disease). Enteroaggregative E. coli causes traveller's diarrhoea and prolonged diarrhoea in undernourished persons. See also Diarrhoeal Diseases Caused by Microbes.
- Viruses and fungi extremely rarely cause prolonged diarrhoea. Cytomegalovirus may cause prolonged diarrhoea in immunosuppressed patients Infections in Immunosuppressed and Cancer Patients.
Abdominal radiotherapy
Ischaemic colitis: the patient often has atherosclerosis, peripheral arterial disease and heart failure together with hypovolaemia due to diuretics, for example. The onset of the disease is usually acute: cramping abdominal pain with blood in the stools. Ischaemic colitis is usually reversible but in severe cases it may cause ulceration, a stricture or perforation.
Functional diarrhoea is a condition in which stools are loose or watery in 75% of bowel movements. This disease is distinguished from diarrhoea-predominant IBS by the lack of abdominal pain.

Causes of prolonged diarrhoea

Watery diarrhoea	Inflammatory diarrhoea	Fatty diarrhoea
Common causes:
Irritable bowel syndrome Functional Bowel Disorders and the Irritable Bowel Syndrome (IBS)	Diverticulitis	Abdominal angina
Ulcerative colitis Ulcerative Colitis	Ulcerative colitis Ulcerative Colitis	Short-bowel syndrome
Crohn's disease Crohn's Disease	Crohn's disease Crohn's Disease	Sequela to bariatric surgery Bariatric Surgery (Obesity Surgery)
Microscopic colitis	Malignant intestinal tumour Colorectal Cancer	Whipple's disease
Coeliac disease Coeliac Disease	Ischaemic colitis	Severe coeliac disease Coeliac Disease
Tumour of the large intestine Colorectal Cancer	Radiation colitis	Biliary tract obstruction
Carbohydrate malabsorption (lactose Lactose Intolerance, fructose)	Intestinal bacterial or parasitic infection Diarrhoeal Diseases Caused by Microbes	Pancreatic exocrine insufficiency Pancreatic Insufficiency
Hyperthyroidism Hyperthyroidism	Intestinal viral infection (CMV, HSV)
Bacterial toxins
Drugs
Alcohol abuse
Laxative abuse
Rarer causes:
Bile acid malabsorption
Sequela of vagotomy or sympathectomy
Eosinophilic gastroenteritis
Diabetic neuropathy Diabetic Neuropathy
Addison's disease Addison's Disease and other Conditions Inducing Hypocortisolism
Autoimmune enteropathy
Vasculitis Vasculitides
Lymphoma Lymphomas
Amyloidosis Amyloidosis
Phaeochromocytoma Rare Endocrine Tumours, gastrinoma Rare Endocrine Tumours, carcinoid syndrome Rare Endocrine Tumours, somatostatinoma Rare Endocrine Tumours, VIPoma Rare Endocrine Tumours

Examination

Patient history

The patient should be examined systematically, considering the individual symptoms.
In diarrhoea, the frequency of bowel movements is increased and the consistency of faeces is looser. Faecal consistency is assessed using the Bristol stool scale http://en.wikipedia.org/wiki/Bristol_stool_scale, where types 6 and 7 mean diarrhoea.
The normal amount of faeces in people on a western diet is about 100 g daily. In people on a diet high in fibre, it may be as high as 300 g daily.
In western countries, chronic diarrhoea means diarrhoea continuing for more than four weeks.
Onset and duration of diarrhoea
- Infectious colitis usually starts acutely with fever and general symptoms. In most cases, infectious colitis does not become chronic.
- Inflammatory bowel diseases and microscopic colitis usually start subacutely or slowly unless triggered by an infection.
- Prolonged diarrhoea with asymptomatic periods suggests a functional disorder (IBS) or microscopic colitis.
Other significant history
- Blood in stools (disease of the large intestine)
- Travel history; prolonged diarrhoea starting after foreign travel requires more extensive microbiological investigations.
- HIV risk factors
- Weight loss
- Faecal incontinence
- Diarrhoea during fasting or at night (often suggests secretory diarrhoea)
- GI disorders in near relatives (IBD, coeliac disease)
- Diarrhoeal volume (in diseases of the small intestine high, in diseases of the large intestine low)
- General symptoms (IBD: fever, joint symptoms, aphthae in the mouth, ophthalmia, skin lesions)
- Drugs
- Use of herbal medicinal products or nutritional supplements
- Diet (lactose, sweeteners, such as sorbitol and xylitol, alcohol)
- Sexual behaviour (anal intercourse)
- Recurrent bacterial infections (immunoglobulin deficiency)
- Intestinal surgery
- Radiotherapy

Laboratory tests

Table T2 lists laboratory tests to define the aetiology of diarrhoea that are suitable for primary health care and specialized care.

Laboratory tests for patients with diarrhoea

Tests in primary health care	Conditions with abnormal results	Tests in specialized care	Conditions with abnormal results
Full blood count	Blood dyscrasias (leukaemia Chronic Myelogenous Leukaemia (CML) Chronic Lymphocytic Leukaemia (CLL) lymphoma Lymphomas)	Faecal elastase 1	Pancreatic exocrine insufficiency Pancreatic Insufficiency
ESR, CRP	Colitis Ulcerative Colitis, ileitis, vasculitis Vasculitides, malignancy Colorectal Cancer	Faecal alpha-1-antitrypsin	Protein-losing enteropathy
Na, K, Crea, serum cortisol	Addison's disease Addison's Disease and other Conditions Inducing Hypocortisolism, dehydration	Plasma gastrin	Zollinger-Ellison syndrome
AST, ALT, ALP	Biliary tract obstruction, excessive alcohol consumption. See Assessing patients with abnormal liver function test results Assessing a Patient with an Abnormal Liver Function Test Result	Radiological bile acid absorption test	Bile acid malabsorption
Blood glucose	Diabetes Type 1 Diabetes: Treatment Comprehensive Treatment and Follow-Up of Type 2 Diabetes, somatostatinoma Rare Endocrine Tumours	Plasma somatostatin	Somatostatinoma Rare Endocrine Tumours
TSH, free T4	Thyroid disorders Hypothyroidism Hyperthyroidism	Plasma chromogranin A	Neuroendocrine tumour Rare Endocrine Tumours
Tissue transglutaminase antibodies	Coeliac disease Coeliac Disease	Plasma VIP	VIPoma Rare Endocrine Tumours
Genetic test for lactose intolerance	Lactose intolerance Lactose Intolerance	24-hour urine metanephrine and normetanephrine	Phaeochromocytoma Rare Endocrine Tumours
Faecal calprotectin	Chronic inflammatory bowel disease Ulcerative Colitis Crohn's Disease	Plasma immunoglobulins	Hypo-/agammaglobulinaemia Susceptibility to Infections in Adults
Faecal nucleic acid detection test (including Salmonella, Shigella, Yersinia, Campylobacter, and types of E. coli that cause diarrhoea) and, if possible, bacterial culture of positive findings	Bacterial gastroenteritis Acute Diarrhoeal Disease in a Traveller	Anti-enterocyte antibodies	Autoimmune enteropathy
Clostridioides gene amplification test	Clostridioides infection Clostridioides Difficile Diarrhoea
Faecal parasites (microscopy or nucleic acid detection test)	Parasitic infection Introduction to Intestinal Protozoal Diseases
HIV antibodies	HIV infection HIV Infection

Diagnostic clues

Age

In young and middle-aged patients prolonged diarrhoea is often functional, caused by malabsorption, or a result of food intolerance. Bloating, abdominal pain, flatulence and mucorrhea together with diarrhoea of varying severity are consistent with the irritable bowel syndrome.
Inflammatory bowel diseases often occur in young people. Bloody diarrhoea is the most important symptom of ulcerative colitis. In Crohn's disease the symptoms may include diarrhoea, abdominal pain, fever and weight loss.
In the elderly, systemic diseases and malignancies should be considered in addition to the aforementioned conditions.

Blood in the stools

Prolonged bloody diarrhoea may be caused by ulcerative colitis, Crohn's disease, ischaemic or radiation colitis, rectal tumour or vasculitis.
Prolonged non-bloody diarrhoea may be caused by an inflammatory bowel disease (Crohn's disease), microscopic colitis, bile acid malabsorption, irritable bowel syndrome, lactose intolerance, coeliac disease, chronic pancreatitis or pancreatic insufficiency, drugs, tumours (intestinal lymphoma, villous adenoma, neuroendocrine tumour).

Fever and elevated infection parameters

Fever and elevated CRP and ESR are often present in the early stages of infectious diarrhoea and in Crohn's disease.
In ulcerative colitis these findings are usually seen only in severe forms of the disease.
In elderly patients, Clostridioides difficile infection often causes a severe general disease that may be associated with fever and increased CRP concentration.

Small volume of stools and frequent defecation

Suggestive of distal colitis or proctitis
There is blood or mucus on the surface of the stools.
The primary investigations include endoscopy and biopsy.
- Ulcerative colitis at an early stage may be difficult to differentiate from infectious colitis, but histology is often helpful.
- Biopsy is mandatory, even if endoscopy findings are normal; microscopic colitis is detected only by histological examination.

Large volume of stools, weight loss and anaemia

Suggestive of proximal bowel disease or malabsorption
Pain around the umbilicus and in the right lower quadrant suggests proximal bowel disease.
Prolonged watery diarrhoea with a varying course may also be caused by collagen colitis or lymphocytic colitis; in these conditions there are no general symptoms or weight loss. Bile acid diarrhoea does not usually involve general symptoms or weight loss, either.
Further investigations should be performed to detect lactose intolerance Lactose Intolerance, coeliac disease Coeliac Disease, ulcerative colitis Ulcerative Colitis, Crohn's disease Ulcerative Colitis, bile acid malabsorption and pancreatic insufficiency Pancreatic Insufficiency.

Abnormal physical findings

Dermatitis herpetiformis may indicate coeliac disease Coeliac Disease.
Nervousness and eye symptoms may be due to hyperthyroidism Hyperthyroidism.
Joint symptoms and erythema nodosum Erythema Nodosum may be associated with chronic inflammatory bowel disease Ulcerative Colitis Crohn's Disease.
Anal incontinence may be due to diminished sphincter tone Faecal Incontinence.
Surgical scars on the abdomen may indicate sequelae of bowel resection.
Enlarged lymph nodes may be associated with lymphoma Lymphomas, other malignant tumour or HIV infection HIV Infection.
Hepatomegaly may be due to a tumour or to amyloidosis Amyloidosis.
Flushing Episodic Attacks of Flushing may be due to the carcinoid syndrome Rare Endocrine Tumours.
Hyperpigmentation may suggest Addison's disease Addison's Disease and other Conditions Inducing Hypocortisolism.

Treatment

Treatment of the underlying cause.
Disturbances of the fluid and electrolyte balance are corrected with parenteral or oral replacement fluid.
Dietary avoidance of food substances that cause diarrhoea (e.g. fructose, sorbitol, caffeine), lactose-free diet trial, avoidance of alcohol
For functional diarrhoea, loperamide can be used (its use should be avoided in infectious diarrhoea and in severe inflammatory bowel disease), as well as added dietary fibre.
Pharmaceuticals intended for symptomatic treatment of diarrhoea are divided in the following groups.
- Drugs that slow down bowel transit: loperamide, tricyclic antidepressants, serotonin (5-HT3) antagonists
- Racecadotril (enkephalinase inhibitor)
- Drugs acting inside the bowel lumen (medicinal fibre, cholestyramine, activated charcoal, bismuth)
- Pro-absorptive substances (clonidine: diabetic diarrhoea)
- Antisecretory drugs (octreotide: diabetic diarrhoea, severe idiopathic diarrhoea, short-bowel syndrome, chemotherapy-induced diarrhoea, AIDS-related diarrhoea, carcinoid diarrhoea, dumping syndrome)

Serious symptoms and signs contraindicating simple monitoring and therapeutic trials

Repeated bloody stools
Weight loss, fever, deterioration of general condition
Acute onset and continuous worsening
Diarrhoea that also occurs at night
Onset of symptoms in old age
Abnormal results of laboratory tests (haemoglobin, ESR, CRP, liver enzymes, faecal blood, faecal calprotectin)
- Laboratory test results are usually normal in functional disorders, lactose malabsorption and microscopic colitis.

Indications for specialist consultation

If gastroscopy is needed and not available in primary care
Suspected ulcerative colitis or Crohn's disease
Persistently severe symptoms despite treatment, or unclear diagnosis

References

Arasaradnam RP, Brown S, Forbes A et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut 2018;67(8):1380-1399. [PubMed]
Trinh C, Prabhakar K. Diarrheal diseases in the elderly. Clin Geriatr Med 2007 Nov;23(4):833-56, vii. [PubMed]
Fine KD, Schiller LR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology 1999;116(6):1464-86. [PubMed]
Schiller LR. Diarrhea and malabsorption in the elderly. Gastroenterol Clin North Am 2009;38(3):481-502. [PubMed]
Schiller LR. Definitions, pathophysiology, and evaluation of chronic diarrhoea. Best Pract Res Clin Gastroenterol 2012;26(5):551-62. [PubMed]
Kaiser L, Surawicz CM. Infectious causes of chronic diarrhoea. Best Pract Res Clin Gastroenterol 2012;26(5):563-71. [PubMed]
Li Z, Vaziri H. Treatment of chronic diarrhoea. Best Pract Res Clin Gastroenterol 2012;26(5):677-87. [PubMed]
Tack J. Functional diarrhea. Gastroenterol Clin North Am 2012;41(3):629-37. [PubMed]
Camilleri M. Bile Acid diarrhea: prevalence, pathogenesis, and therapy. Gut Liver 2015;9(3):332-9. [PubMed]
Schiller LR, Pardi DS, Spiller R et al. Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea: definition, classification, diagnosis. J Gastroenterol Hepatol 2014;29(1):6-25. [PubMed]
Schiller LR, Pardi DS, Sellin JH. Chronic Diarrhea: Diagnosis and Management. Clin Gastroenterol Hepatol 2017;15(2):182-193.e3. [PubMed]