What are the causes and treatment options for recurrent diarrhea?

Recurrent Diarrhea: Causes and Differential Diagnosis

Immediate Clinical Triage

Patients with recurrent diarrhea require immediate physician evaluation if they are elderly (>75 years), have concomitant significant systemic illnesses, chronic bowel disease, or are frail, rather than attempting self-management. 1

Red Flag Symptoms Requiring Urgent Gastroenterology Referral

• Blood in stool 2
• Unintentional weight loss 2
• Clinical and laboratory signs of anemia 2
• Palpable abdominal mass 2
• High fever (>38.5°C) 1
• Severe vomiting leading to rapid dehydration 1
• Obvious dehydration 1

Infectious Causes

Bacterial Pathogens

• Clostridium difficile is of increasing concern, particularly in patients with recent antimicrobial therapy 3
• Recurrent C. difficile infection (≥2 episodes) warrants fecal microbiota-based therapies after completing standard antibiotics 1
• Important bacterial causes include Salmonella, Shigella, Yersinia, Campylobacter, and pathogenic E. coli strains 3
• Enteroaggregative E. coli can cause persistent symptoms 4
• Yersinia, Plesiomonas, and Aeromonas are rare bacterial causes of chronic diarrhea in immunocompetent individuals 5

Viral Pathogens

• Norovirus is the most common cause of diarrheal disease outbreaks and acute gastroenteritis across all age groups 3
• Chronic and severe norovirus infection occurs in immunosuppressed patients following organ transplantation 3

Parasitic Pathogens

• Common parasites causing recurrent diarrhea include Giardia, Cryptosporidium, and Entamoeba histolytica 3
• Approximately 10% of traveler's diarrhea is parasitic, persisting for weeks to months, with giardiasis being most common 3
• Cyclospora and Cystoisospora are additional parasitic causes 3
• Critical pitfall: Standard ova and parasite testing often excludes Cryptosporidium and Cyclospora—clinicians must specifically request these tests 3

Non-Infectious Causes

Gastrointestinal Disorders

• Irritable bowel syndrome with diarrhea (IBS-D) is a common functional disorder requiring Rome III criteria for diagnosis 6
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) can present with recurrent diarrhea 7
• Post-infectious irritable bowel syndrome can develop after infectious diarrhea 1
• "Brainerd-type" diarrhea can be triggered by infectious episodes 5

Malabsorption Syndromes

• Celiac disease is the most common small bowel enteropathy in Western populations, frequently presenting with steatorrhea (pale, bulky, malodorous stools) 3, 7
• Chronic pancreatitis is the primary cause of severe steatorrhea, requiring approximately 90% destruction of pancreatic tissue before symptoms appear, with fecal fat >13 g/day 3, 7
• Bile acid malabsorption produces diarrhea characteristically occurring after meals and responding to fasting, particularly common after terminal ileum resection or cholecystectomy 3, 7

Endocrine Causes

• Hyperthyroidism causes diarrhea through endocrine effects on gut motility 3, 7
• Diabetes mellitus causes diarrhea via multiple mechanisms: autonomic neuropathy, bacterial overgrowth, bile acid malabsorption, and medication effects 3, 7

Medication-Related

• Adverse effects of antiretroviral therapy or chemotherapy may account for persistent diarrhea in immunocompromised hosts 3
• Medications including magnesium-containing products, NSAIDs, antibiotics, and antiarrhythmics account for up to 4% of chronic diarrhea cases 7

Special Populations

Immunocompromised Patients

• HIV-infected patients are at risk for enteroaggregative E. coli, Cryptosporidium, microsporidia, Cystoisospora belli, CMV, and Mycobacterium avium complex 3
• Diarrhea caused by Cryptosporidium, Cyclospora, Cystoisospora, or microsporidia is more likely to be severe, chronic, or relapsing in patients with impaired cell-mediated immunity 3
• In patients with diarrhea lasting ≥30 days, HIV testing may be appropriate 3

High-Risk Groups for Specific Pathogens

• Risk factors for invasive nontyphoidal Salmonella include young and advanced age, HIV infection, cytotoxic chemotherapy, malnutrition, hemoglobinopathies, recent malaria, and cirrhosis 3
• Yersinia enterocolitica higher risk groups include young African American and Asian children, diabetics, and those with chronic liver disease, malnutrition, or iron-overload states 3
• Vibrio vulnificus infections occur in patients with chronic liver disease, iron overload states, or other immunocompromising conditions 3

Diagnostic Approach

When to Test

Perform selective fecal studies in patients with: 1

• Signs of severe dehydration 1
• Bloody stools 1
• Persistent fever 1
• Immunodeficiencies or immunosuppressive therapy 1
• Suspected nosocomial infection 1

Diagnostic Testing Options

• Culture-dependent methods for bacterial pathogens 4
• Culture-independent methods including PCR and multiplex PCR for bacterial, viral, and protozoal infections 4
• Microscopy for protozoal infections 4
• Pitfall: Multipathogen nucleic acid amplification tests can detect multiple pathogens simultaneously, but the clinical significance of detecting multiple pathogens or nucleic acid alone (versus viable organisms) remains unclear 3
• Fecal lactoferrin testing or microscopy for leukocytes can document inflammation in invasive colitis, severe C. difficile colitis, and inflammatory bowel disease 1

Clinical Clues

• Normal vital signs and physical examination despite reported severe symptoms are consistent with factitious diarrhea 3
• Diarrhea alternating with constipation or no response to vancomycin/fidaxomicin suggests alternative diagnoses to C. difficile recurrence 1

Treatment Principles

When NOT to Treat Empirically

• In most people with acute watery diarrhea without recent international travel, empiric antimicrobial therapy is not recommended 1
• Empiric treatment should be avoided in people with persistent watery diarrhea lasting ≥14 days 1
• Asymptomatic contacts should not receive empiric or preventive therapy 1

Supportive Care

• Reduced osmolarity oral rehydration solution (ORS) is first-line therapy for mild to moderate dehydration 1
• Isotonic intravenous fluids (lactated Ringer's, normal saline) should be administered for severe dehydration, shock, altered mental status, or ORS failure 1
• Human milk feeding should be continued throughout the diarrheal episode in infants and children 1
• Resume age-appropriate usual diet during or immediately after rehydration 1

Antimotility Agents

• Antimotility drugs (e.g., loperamide) should NOT be given to children <18 years of age with acute diarrhea 1
• Loperamide may be given to immunocompetent adults with acute watery diarrhea 1
• Antimotility drugs should be avoided with bloody diarrhea or proven Shiga toxin-producing E. coli infection 1

Specific Therapies

• Antimicrobial therapy should be modified or discontinued when a clinically plausible organism is identified 1
• For recurrent C. difficile infection (≥2 episodes), fecal microbiota-based therapies should be given upon completion of standard antibiotics 1
• Rifaximin 550 mg three times daily for 14 days is FDA-approved for IBS-D in adults meeting Rome criteria 6