What is the best course of action for a patient with recurrent diarrhea that has been waxing and waning for 2 weeks after initial resolution?

Management of Waxing and Waning Diarrhea After Initial Resolution

For a patient with diarrhea that resolved after 2 weeks but is now recurring in a waxing and waning pattern, you should conduct a clinical and laboratory reevaluation to exclude both persistent infectious causes and noninfectious conditions, particularly inflammatory bowel disease (IBD) and post-infectious irritable bowel syndrome (IBS), as symptoms lasting ≥14 days warrant consideration of these underlying etiologies. 1

Initial Assessment and Red Flags

Obtain a detailed history focusing on:

• Stool characteristics: frequency, consistency (watery vs. bloody), nocturnal symptoms, and volume 1
• Alarm features that mandate urgent evaluation: blood in stool, unintentional weight loss, fever, signs of dehydration (dizziness upon standing), or severe abdominal pain 1, 2
• Travel history, dietary exposures (raw/undercooked meat, seafood, unpasteurized dairy), daycare attendance, sick contacts, and sexual practices 1
• Medication review to identify potential diarrheogenic agents 1
• Surgical history (particularly bowel resections that can cause bile acid diarrhea or bacterial overgrowth) 1
• Systemic diseases: thyroid disorders, diabetes, or immunocompromising conditions 1

Physical examination should assess:

• Hydration status and vital signs (orthostatic changes) 1
• Abdominal examination for masses, tenderness, or distension 2

Diagnostic Workup

Since symptoms have persisted beyond 14 days with a waxing and waning pattern, testing is indicated: 1

First-line laboratory studies:

• Stool studies: culture for bacterial pathogens (Salmonella, Shigella, Campylobacter, STEC), ova and parasites, Clostridioides difficile testing if risk factors present 1
• Blood tests: complete blood count (to assess for anemia or leukocytosis), comprehensive metabolic panel (electrolytes, renal function), thyroid function tests, celiac serology (tissue transglutaminase IgA with total IgA) 1
• Fecal calprotectin or lactoferrin if inflammatory bowel disease is suspected 1

The 2017 IDSA guidelines emphasize that noninfectious conditions, including IBD and post-infectious IBS, should be strongly considered as underlying etiologies in people with symptoms lasting ≥14 days with unidentified sources. 1 This is a critical distinction because the waxing and waning pattern after initial resolution suggests either persistent infection with intermittent shedding, post-infectious functional changes, or an underlying inflammatory condition that was unmasked by the initial infectious episode.

Management Strategy

Rehydration remains the cornerstone:

• Reduced osmolarity oral rehydration solution (ORS) for mild to moderate dehydration 1
• Intravenous fluids (lactated Ringer's or normal saline) only if severe dehydration, shock, altered mental status, or ORS failure 1

Dietary modifications:

• Eliminate lactose-containing products (lactose intolerance can develop post-infectious diarrhea), alcohol, caffeine, and high-osmolar supplements 1, 3
• Small frequent meals with easily digestible foods (bananas, rice, applesauce, toast, plain pasta) 1, 3
• Maintain hydration with 8-10 glasses of clear liquids daily 3

Empiric antimicrobial therapy is NOT recommended for persistent watery diarrhea lasting ≥14 days without specific pathogen identification, as this duration makes acute bacterial infection less likely and risks selecting for resistant organisms. 1 The exception would be if stool studies identify a specific treatable pathogen.

Symptomatic management:

• Loperamide may be considered in immunocompetent adults with watery (non-bloody) diarrhea without fever: initial dose 4 mg, then 2 mg after each unformed stool (maximum 16 mg/day) 1, 4
• Avoid loperamide if there is any suspicion of inflammatory diarrhea, bloody stools, or fever, as this can precipitate toxic megacolon 1
• Probiotics may reduce symptom severity and duration in immunocompetent patients 1

When to Escalate Care

Refer for gastroenterology evaluation if: 1, 2

• Alarm features are present (blood in stool, weight loss, anemia, palpable abdominal mass)
• Symptoms persist despite initial management and negative infectious workup
• Quality of life is significantly impaired
• Suspicion for IBD, celiac disease, or other chronic conditions requiring endoscopic evaluation

Consider endoscopy with biopsies if symptoms persist beyond 4 weeks with negative stool studies, as this can diagnose microscopic colitis, IBD, celiac disease, or other mucosal pathology. 1

Common Pitfalls to Avoid

• Do not assume resolution means cure: The initial 2-week resolution followed by recurrence suggests either relapsing infection (parasites like Giardia or Cryptosporidium), post-infectious IBS, or unmasking of underlying IBD 1
• Do not overlook bile acid diarrhea: If the patient has had prior ileal resection or cholecystectomy, empiric trial of bile acid sequestrants may be diagnostic and therapeutic 1
• Do not continue empiric antibiotics without pathogen identification in persistent diarrhea, as this can worsen outcomes and promote resistance 1
• Reassess fluid and electrolyte balance, nutritional status regularly in patients with persistent symptoms 1

The waxing and waning pattern after initial resolution is the key clinical clue that distinguishes this from simple acute infectious diarrhea and mandates a broader differential diagnosis including post-infectious functional disorders and chronic inflammatory conditions.