Diarrhea, Chronic

For further information, see CMDT Part 15-06: Diarrhea

Essentials of Diagnosis

• Diarrhea present for > 4 weeks

• Before embarking on extensive work up, common causes should be excluded, including medications, chronic infections, and irritable bowel syndrome

• Classification

  • Medications

  • Osmotic diarrhea

  • Secretory conditions

  • Inflammatory conditions

  • Malabsorption conditions

  • Motility disorders

  • Chronic infections

  • Systemic disorders

General Considerations

• Medications that can commonly cause diarrhea include

  • Cholinesterase inhibitors

  • Selective serotonin reuptake inhibitors

  • Angiotensin II-receptor blockers

  • Proton pump inhibitors

  • Nonsteroidal anti-inflammatory drugs

  • Metformin

  • Allopurinol

  • Orlistat

• Osmotic diarrheas resolve during fasting

• Secretory diarrhea is caused by increased intestinal secretion or decreased absorption with little change in stool output during fasting

• The major causes of malabsorption are small intestinal mucosal diseases, intestinal resections, lymphatic obstruction, small intestinal bacterial overgrowth, and pancreatic insufficiency

• Motility disorders are secondary to systemic disorders, radiation enteritis, or surgery that lead to rapid transit or to stasis of intestinal contents with bacterial overgrowth, malabsorption

• Immunocompromised patients are susceptible to Microsporidia, Cryptosporidium, cytomegalovirus, Isospora belli, Cyclospora, and Mycobacterium avium-intracellulare infections

• Chronic systemic conditions such as thyroid disease, diabetes, and collagen vascular disorders may cause diarrhea through alterations in motility or intestinal absorption

Demographics

• Lactase deficiency

  • Occurs in 75% of nonwhite adults and 25% of whites

  • May be acquired with viral gastroenteritis, medical illness, or gastrointestinal surgery

Symptoms and Signs

• Osmotic diarrheas

  • Abdominal distention

  • Bloating

  • Flatulence due to increased colonic gas production

• Secretory diarrhea

  • High-volume (> 1 L/day) watery diarrhea

  • Dehydration

  • Electrolyte imbalance

• Inflammatory conditions

  • Abdominal pain

  • Fever

  • Weight loss

  • Hematochezia

• Malabsorption syndromes

  • Weight loss

  • Osmotic diarrhea

  • Steatorrhea

  • Nutritional deficiencies

Differential Diagnosis

• Common

  • Irritable bowel syndrome

  • Parasites

  • Caffeine

  • Laxative abuse

• Osmotic

  • Lactase deficiency

  • Medications: antacids, lactulose, sorbitol, olestra

  • Factitious: magnesium-containing antacids or laxatives

• Secretory

  • Hormonal: Zollinger-Ellison syndrome (gastrinoma), carcinoid, VIPoma, medullary thyroid carcinoma, adrenal insufficiency

  • Laxative abuse: cascara, senna

  • Medications

  • Microscopic colitis

• Inflammatory conditions

  • Inflammatory bowel disease

  • Cancer with obstruction and pseudodiarrhea

  • Radiation colitis

• Malabsorption

  • Small bowel: celiac disease, Whipple disease, tropical sprue, eosinophilic gastroenteritis, small bowel resection, Crohn disease

  • Lymphatic obstruction: lymphoma, carcinoid, tuberculosis, M avium-intracellulare infection, Kaposi sarcoma, sarcoidosis, retroperitoneal fibrosis

  • Pancreatic insufficiency: chronic pancreatitis, cystic fibrosis, pancreatic cancer

  • Bacterial overgrowth, eg, diabetes

  • Reduced bile salts: ileal resection, Crohn disease, postcholecystectomy

• Motility disorders

  • Irritable bowel syndrome

  • Postsurgical: vagotomy, partial gastrectomy, blind loop with bacterial overgrowth

  • Systemic disease: diabetes mellitus, hyperthyroidism, scleroderma

  • Caffeine or alcohol use

• Chronic infections

  • Parasites: giardiasis, amebiasis, strongyloidiasis

Laboratory Tests

• Obtain complete blood count, serum electrolytes, liver biochemical tests, calcium, phosphorus, albumin, thyroid-stimulating hormone

• INR, erythrocyte sedimentation rate, and C-reactive protein should be obtained in most patients

• Serologic testing for celiac disease with the IgA tissue transglutaminase antibody test may be recommended for most patients with chronic diarrhea and all patients with signs of malabsorption

• Stool studies

  • Analyze stool sample for ova and parasites, electrolytes (to calculate osmotic gap), qualitative staining for fat (Sudan stain), occult blood, and leukocytes or lactoferrin

  • The presence of fecal leukocytes or lactoferrin may suggest inflammatory bowel disease

  • Parasitic infections (Giardia, Entamoeba histolytica, Cryptosporidia, and Cyclospora) may be diagnosed with stool antigen assays or microscopy with special stains

  • Alternatively, stool molecular diagnostic tests are available that screen for a panel of pathogens, providing results within 5 hours

  • An increased osmotic gap suggests an osmotic diarrhea or disorder of malabsorption

  • A positive fecal fat stain suggests a disorder of malabsorption

  • 24-hour stool collection for weight and quantitative fecal fat

    • Stool weight < 200–300 g/24 h excludes diarrhea and suggests a functional disorder such as irritable bowel

    • Stool weight > 200 g/24 hours confirms diarrhea

    • Stool weight > 1000–1500 g/24 hours suggests secretory diarrhea, including neuroendocrine tumors

    • Fecal fat > 10 g/24 hours indicates a malabsorption syndrome

• If malabsorption suspected

  • Obtain serum folate, B₁₂, iron, vitamin A and D, prothrombin time

  • Serologic test for celiac disease: serum IgA tissue transglutaminase antibody test

• If secretory cause suspected

  • Obtain serum VIP (VIPoma), chromogranin A (carcinoid), calcitonin (medullary thyroid carcinoma), gastrin (Zollinger-Ellison syndrome), and glucagon

  • Obtain urine 5-hydroxyindoleacetic acid (carcinoid)

Imaging Studies

• Abdominal CT for suspected chronic pancreatitis, pancreatic cancer, neuroendocrine tumors

• Small intestinal imaging with CT, MRI, or enterography is helpful in the diagnosis of Crohn disease, small bowel lymphoma, carcinoid, and jejunal diverticula

• Somatostatin receptor scintigraphy in suspected neuroendocrine tumors

Diagnostic Procedures

• Sigmoidoscopy or colonoscopy with mucosal biopsy to diagnose inflammatory bowel disease and melanosis coli

• Upper endoscopy with small bowel biopsy to diagnose suspected celiac sprue, Whipple disease, and AIDS-related Cryptosporidium, Microsporidia, and M avium-intracellulare infection

• Breath hydrogen tests

  • Can suggest diagnosis of small bowel bacterial overgrowth

  • However, a high-rate of false-positive results limits usefulness

• Aspirate of small intestinal contents for quantitative aerobic and anaerobic bacterial culture

  • Offers definitive diagnosis of bacterial overgrowth

  • However, this procedure is not available at most centers

Medications

• Loperamide: 4 mg orally initially, then 2 mg after each loose stool (maximum: 8 mg/day)

• Diphenoxylate with atropine: 1 tablet three or four times daily orally as needed

• Codeine 15–60 mg every 4 hours orally; tincture of opium, 0.03–1.2 mL every 6 hours as needed, safe in most patients with chronic, intractable diarrhea

• Clonidine, 0.1–0.3 mg twice daily orally, or a clonidine patch, 0.1–0.2 mg/day, helpful in secretory diarrheas, diabetic diarrhea, and cryptosporidiosis

• Octreotide, 50 mcg to 250 mcg three times daily subcutaneously, for secretory diarrheas due to neuroendocrine tumors (VIPomas, carcinoid); a once monthly depot formulation is available

• Cholestyramine or colestipol (2–4 g once to three times daily) or colesevelam (625 mg, 1–3 tablets once or twice daily) in patients with bile salt–induced diarrhea, which may be idiopathic or secondary to intestinal resection or ileal disease

Therapeutic Procedures

• Consider discontinuing medications that could be causing chronic diarrhea

Complications

• Dehydration

• Electrolyte abnormalities

• Malabsorption: weight loss, vitamin deficiencies

Prognosis

• Cause is identifiable and treatable in almost all patients

When to Admit

• Secretory diarrhea with dehydration