What is the best course of treatment for a patient with chronic diarrhea, acid reflux, and intermittent rash, presenting with elevated inflammatory markers, increased intestinal permeability, and intestinal yeast?

Management of Chronic Diarrhea with Elevated Inflammatory Markers and Intestinal Permeability

This patient requires immediate systematic evaluation to rule out inflammatory bowel disease (IBD) or other organic pathology, followed by targeted treatment of identified intestinal yeast overgrowth and barrier dysfunction, with proton pump inhibitors for acid reflux symptoms. 1

Immediate Diagnostic Priorities

The constellation of chronic progressive diarrhea (now nocturnal), elevated inflammatory markers, increased intestinal permeability, and intestinal yeast demands urgent exclusion of active inflammatory disease before attributing symptoms to functional causes:

• Measure fecal calprotectin immediately to assess for ongoing intestinal inflammation, as this is the only biomarker approved by ECCO for distinguishing organic from functional disease 1, 2
• Perform colonoscopy with biopsies to evaluate for IBD, microscopic colitis, or other mucosal pathology, as endoscopic assessment with histopathology remains the gold standard 1, 3
• Obtain cross-sectional imaging (CT or MRI enterography) to assess for structural complications, small bowel involvement, or anatomic abnormalities 1

The elevated LDH, ferritin, B12, and basophils alongside inflammatory markers suggest either active inflammation or a systemic process that requires definitive characterization before empiric treatment 3.

Address Identified Pathology

Intestinal Yeast Overgrowth

The documented intestinal yeast on stool sample requires antifungal therapy, though evidence for this in chronic diarrhea is limited outside specific immunocompromised contexts 4. Consider fluconazole or nystatin while awaiting definitive IBD workup.

Acid Reflux Management

Initiate proton pump inhibitor therapy for symptomatic acid reflux, as this is standard first-line treatment and particularly important if gastroduodenal Crohn's disease is identified 3

Increased Intestinal Permeability

While increased intestinal permeability is associated with persistent diarrhea and abdominal pain even with mucosal healing in IBD patients, it is not yet an established therapeutic target 3. The permeability may normalize with treatment of underlying inflammation 5, 6.

Evaluate Alternative Mechanisms

If initial workup excludes active IBD or other organic disease, systematically assess these common causes of persistent diarrhea:

• Small intestinal bacterial overgrowth (SIBO): Perform glucose or lactulose hydrogen breath testing, particularly given the intestinal yeast finding suggesting dysbiosis 3
• Bile acid diarrhea: Consider SeHCAT scan or empiric trial of bile acid sequestrants (cholestyramine 4g with meals), especially if diarrhea is postprandial 3, 1
• Carbohydrate malabsorption: Breath testing for lactose and fructose intolerance, as these are more frequent in IBD and can persist even in remission 3
• Celiac disease: Serological testing with tissue transglutaminase IgA and total IgA 3

Treatment Algorithm Based on Findings

If Active IBD is Confirmed:

• For mild-moderate disease: Aminosalicylates (mesalazine ≥2g/day) for ulcerative colitis; less effective in Crohn's disease 1
• For moderate-severe or steroid-dependent disease: Immunomodulators (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) with regular FBC monitoring 3, 1
• For refractory disease: Biologic therapy after discussion of risks/benefits and surgical options 3

If Functional Symptoms Predominate (After Excluding Inflammation):

• Dietary modification: Trial of low FODMAP diet with nutritional monitoring, as this addresses carbohydrate malabsorption and has evidence in IBD-related functional symptoms 3, 1
• Symptomatic management:
  • Loperamide for diarrhea control in quiescent disease 1
  • Avoid opiates due to risk of complications 1
• Probiotics: May be considered for functional symptoms and to address dysbiosis 1
• Psychological therapies: Cognitive behavioral therapy or hypnotherapy if anxiety or depression contribute to symptoms 1

Critical Pitfalls to Avoid

Do not attribute symptoms to IBS or functional disease without objective exclusion of inflammation, as nocturnal diarrhea is an alarm feature suggesting organic pathology 3. The progression from chronic to nocturnal diarrhea is particularly concerning and demands thorough evaluation.

Do not escalate immunosuppression if C. difficile infection is identified, as this can worsen outcomes; maintain current immunosuppression but avoid escalation 3

Monitor for complications: The elevated hematocrit may indicate dehydration from chronic diarrhea; the intermittent rash could represent erythema nodosum, pyoderma gangrenosum, or other IBD-associated dermatologic manifestations requiring specific management 3

The combination of systemic laboratory abnormalities (elevated LDH, ferritin, B12, basophils) with progressive GI symptoms necessitates comprehensive evaluation before assuming a benign functional etiology 3, 4.