What is the best approach to evaluate and treat an adult patient with no significant underlying health conditions presenting with diarrhea?

Evaluation of Diarrhea in Adults

Begin with a focused history to distinguish acute from chronic diarrhea (≥4 weeks duration) and identify alarm features that mandate urgent investigation, followed by targeted laboratory and stool testing based on duration and clinical presentation. 1, 2

Initial Clinical Assessment

Key Historical Elements to Elicit

• Duration of symptoms: <4 weeks suggests acute infectious etiology (usually viral, self-limited); ≥4 weeks defines chronic diarrhea requiring systematic evaluation 1, 3, 2
• Alarm features requiring urgent gastroenterology referral: 1, 4
  • Unintentional weight loss
  • Blood in stool (visible or occult)
  • Nocturnal diarrhea
  • Fever >38.5°C
  • Age >45 years with new-onset symptoms
  • Signs of severe dehydration (tachycardia, hypotension, decreased skin turgor, dry mucous membranes) 5
• Medication review: Up to 4% of chronic diarrhea is drug-induced 1
• Dietary history: Lactose-containing products, high-osmolar supplements, recent dietary changes 5, 1
• Surgical history: Prior abdominal/pelvic surgery or radiation 5

Physical Examination Priorities

• Assess hydration status: Heart rate, blood pressure (orthostatic changes), skin turgor, mucous membranes 5
• Abdominal examination: Bowel sounds (hyperactive vs. absent), tenderness, masses, signs of peritonitis 5
• Rectal examination: Exclude perianal abscess, assess for blood or mucus 5

Acute Diarrhea (<4 Weeks)

When to Test vs. Treat Empirically

Most acute diarrhea is viral and self-limited; restrict diagnostic testing to high-risk patients only. 3, 6

Indications for stool studies and laboratory workup: 5, 3

• Severe dehydration requiring IV fluids
• Bloody diarrhea (dysentery)
• Persistent fever
• Immunosuppression or immunosuppressive therapy
• Suspected nosocomial infection or outbreak
• Symptoms >7 days without improvement

Recommended Testing for High-Risk Acute Diarrhea

• Stool studies: Culture for Shigella, Salmonella, Campylobacter, STEC O157:H7; Clostridium difficile testing (especially if recent antibiotics); parasites (Giardia, Cryptosporidium, Entamoeba) if indicated 5, 3
• Blood work: Complete blood count, electrolytes, renal function if severe dehydration or systemic illness 5
• Blood cultures: Minimum two sets if fever with neutropenia or severe illness 5

Treatment Approach for Acute Diarrhea

Oral rehydration with early refeeding is the cornerstone of treatment. 5, 3

• Fluid replacement: Oral rehydration solutions (WHO ORS or commercial preparations) for mild-moderate dehydration 5, 3
• IV fluids: Reserved for severe dehydration; initial bolus 20 mL/kg if tachycardic/potentially septic, then rate exceeding ongoing losses (urine output + 30-50 mL/h insensible losses + GI losses) 5
• Loperamide: 4 mg initially, then 2 mg after each unformed stool (maximum 16 mg/day) for watery diarrhea; avoid in bloody diarrhea 5, 7, 3
• Antibiotics: Reserve for proven bacterial infections (Shigella, Campylobacter, C. difficile, traveler's diarrhea, protozoal infections) 5, 3
• Probiotics: May shorten illness duration 3

Common pitfall: Avoid antimotility agents in bloody diarrhea due to risk of toxic megacolon and worsening outcomes. 5, 7

Chronic Diarrhea (≥4 Weeks)

First-Line Investigations (All Patients)

Perform standardized screening panel before considering functional diagnosis. 5, 1, 2

Blood tests: 5, 1, 2

• Complete blood count (assess anemia, leukocytosis)
• C-reactive protein
• Comprehensive metabolic panel (albumin, electrolytes, renal function)
• Liver function tests
• Iron studies, vitamin B12, folate
• Thyroid function tests
• Anti-tissue transglutaminase IgA with total IgA (mandatory celiac screening)

Stool tests: 5, 1

• Fecal calprotectin (exclude colonic inflammation; elevated >50 suggests organic disease)
• Fecal immunochemical test (FIT) for occult blood
• Stool culture if infectious etiology suspected

Age-Stratified Endoscopic Evaluation

Patients ≥45 years: Full colonoscopy with biopsies is mandatory due to colorectal cancer risk. 5, 1

Patients <40 years without alarm features and normal fecal calprotectin: Can consider positive IBS diagnosis using Rome IV criteria after completing basic screening; defer colonoscopy unless symptoms persist despite treatment 5, 1

Critical colonoscopy technique: Obtain biopsies from right and left colon (not rectum) even if mucosa appears completely normal, as microscopic colitis has normal-appearing mucosa endoscopically 5, 1

Common pitfall: Missing microscopic colitis by failing to biopsy normal-appearing mucosa or by relying on CT imaging alone, which cannot detect microscopic colitis, early IBD, or subtle mucosal abnormalities. 1

Evaluation for Specific Treatable Causes

Bile acid diarrhea: 5, 1

• Diagnose with SeHCAT testing or serum 7α-hydroxy-4-cholesten-3-one
• Do not use empiric trial of bile acid sequestrants without objective testing
• Treat with cholestyramine, colestipol, or colesevelam if confirmed 5

Microscopic colitis: 5, 1

• Requires colonoscopy with biopsies (cannot be diagnosed without histology)
• Treat with budesonide if confirmed 5

Lactose maldigestion: 5

• Hydrogen breath testing if available, or empiric lactose-free diet trial

Small bowel bacterial overgrowth: 5

• Empiric antibiotic trial recommended over breath testing

Pancreatic insufficiency: 5

• Fecal elastase testing when fat malabsorption suspected
• Treat with pancreatic enzyme replacement if confirmed

Advanced Imaging (When Indicated)

MR enterography or video capsule endoscopy: For small bowel evaluation if initial workup negative and symptoms persist 5

Do not use small bowel barium studies due to poor sensitivity and specificity 5

Symptomatic Management

Loperamide is first-line antidiarrheal therapy when appropriate. 7

Loperamide Dosing and Precautions

• Initial dose: 4 mg, then 2 mg after each unformed stool 5, 7
• Maximum: 16 mg/day 5, 7
• Contraindications: 7
  • Bloody diarrhea
  • Suspected C. difficile colitis
  • Acute ulcerative colitis
  • Children <2 years (risk of respiratory depression and cardiac events)
• Avoid in: 7
  • Patients taking CYP3A4 inhibitors (itraconazole), CYP2C8 inhibitors (gemfibrozil), or P-glycoprotein inhibitors (quinidine, ritonavir) due to increased cardiac risk
  • Patients with QT prolongation risk factors or taking QT-prolonging drugs
  • Hepatic impairment (use with caution, monitor for CNS toxicity)

Critical warning: Higher-than-recommended doses can cause QT prolongation, Torsades de Pointes, cardiac arrest, and death. 7

Complicated Diarrhea Requiring Hospitalization

Hospitalize patients with: 5

• Severe dehydration despite oral rehydration
• Sepsis or neutropenia
• Significant GI bleeding
• Severe cramping, vomiting, diminished performance status

Intensive management: 5

• IV fluids and electrolyte replacement
• Octreotide 100-150 mcg SC/IV three times daily (escalate to 500 mcg if needed)
• Empiric fluoroquinolone or metronidazole
• Complete blood count, electrolytes, comprehensive stool workup

Neutropenic Enterocolitis (Special Case)

Initial medical management: 5

• Broad-spectrum antibiotics covering gram-negatives, gram-positives, and anaerobes (piperacillin-tazobactam, imipenem-cilastatin, or cefepime/ceftazidime + metronidazole)
• G-CSF administration
• Nasogastric decompression, IV fluids, bowel rest
• Avoid anticholinergics, antidiarrheals, and opioids (may worsen ileus)
• Consider amphotericin if no response to antibacterials (fungemia common)

Surgical indications: Persistent bleeding after correction of coagulopathy, free perforation, abscess formation, clinical deterioration despite aggressive medical therapy 5

Common Pitfalls to Avoid

• Premature IBS diagnosis: Complete basic blood and stool screening before applying Rome criteria 1
• Over-testing in acute viral diarrhea: Stool cultures have <5% yield in uncomplicated cases 5, 6
• Missing celiac disease: Always include anti-tissue transglutaminase IgA with total IgA 1, 2
• Inadequate colonoscopy: Failing to biopsy normal-appearing mucosa or obtain biopsies from right and left colon 1
• Relying on CT alone: Normal CT does not exclude microscopic colitis, early IBD, or mucosal abnormalities requiring endoscopic diagnosis 1
• Empiric bile acid sequestrant trial: Make objective diagnosis with SeHCAT or serum testing first 5, 1