What is the best course of treatment for a patient with a 3-year history of diarrhea, recently worsened to include nocturnal diarrhea and nasal regurgitation, with findings of hematin in the stomach and duodenum, mild gastritis and esophagitis on EGD (Esophagogastroduodenoscopy), and normal colonoscopy results?

Management of Chronic Diarrhea with Upper GI Findings

This patient requires aggressive acid suppression with a proton pump inhibitor (PPI) and further investigation to exclude small bowel pathology, particularly given the nocturnal symptoms and hematin findings suggesting hyperacidity.

Immediate Therapeutic Intervention

Initiate high-dose PPI therapy immediately to address the hematin, gastritis, and esophagitis documented on endoscopy. 1

• Omeprazole 40 mg once daily is the appropriate starting dose for active gastric pathology, as hematin formation occurs exclusively at pH=1 and represents strong gastric acidity 2
• The presence of hematin throughout the stomach and proximal duodenum indicates severe hyperacidity requiring aggressive acid suppression 2
• Continue PPI therapy for 4-8 weeks initially, as most gastric and duodenal lesions heal within this timeframe 1

Critical Diagnostic Gaps Requiring Urgent Attention

The normal colonoscopy does not explain the 3-year history of worsening diarrhea with nocturnal symptoms, which suggests small bowel pathology that has not been adequately evaluated. 3

Essential Next Steps:

• Obtain duodenal biopsies if not already performed during EGD to exclude celiac disease, as this is a critical cause of chronic diarrhea that requires specific evaluation 3
• Celiac serology (tissue transglutaminase antibodies) should be checked if not already done, though biopsies remain the gold standard 3
• Review capsule endoscopy images systematically for small bowel inflammation, ulceration, or mass lesions beyond the hematin findings 3

Small Bowel Evaluation:

The capsule endoscopy showing hematin and erythema in the proximal duodenum warrants careful interpretation: 2

• Hematin itself represents gastric hyperacidity rather than active bleeding 2
• However, the erythema in the duodenum suggests true inflammatory pathology requiring further characterization 3
• If duodenal biopsies were not obtained during the initial EGD, repeat endoscopy with multiple biopsies from the second portion of the duodenum is mandatory 3

Differential Diagnosis Framework

Most Likely Diagnoses Based on Presentation:

1. Celiac disease - chronic diarrhea with nocturnal symptoms in the context of duodenal inflammation 3
2. Small bowel Crohn's disease - capsule findings of inflammation, chronic progressive symptoms 3
3. Peptic ulcer disease with severe gastritis - hematin findings, though this alone does not explain chronic diarrhea 1, 2
4. Microscopic colitis - though colonoscopy was normal, this requires specific histologic evaluation of normal-appearing mucosa 3

Critical Pitfall to Avoid:

Never accept esophagitis, erosions, and peptic ulcer disease as the sole cause of symptoms until lower GI investigations AND small bowel evaluation have been completed. 3 The presence of upper GI pathology should not deter comprehensive evaluation when chronic diarrhea is the primary complaint.

Additional Investigations Required

If Celiac Disease is Excluded:

• Stool studies: fecal calprotectin to assess for inflammatory bowel disease, stool culture and ova/parasites, Giardia ELISA 3
• Consider Helicobacter pylori testing if not already performed, as colonization may impair iron uptake and contribute to symptoms 3
• Small bowel MRI or CT enterography if capsule endoscopy findings are equivocal or suggest Crohn's disease 3

Specific Testing Based on Nocturnal Symptoms:

Nocturnal diarrhea is a red flag suggesting organic rather than functional disease: 3

• This symptom pattern makes irritable bowel syndrome unlikely 3
• Suggests secretory diarrhea or inflammatory bowel disease requiring definitive diagnosis 3
• The nasal regurgitation while sleeping suggests severe gastroesophageal reflux requiring aggressive PPI therapy 1

Monitoring and Follow-Up Strategy

Short-term (4-8 weeks):

• Reassess symptoms on PPI therapy - expect improvement in reflux, nasal regurgitation, and upper GI symptoms 1
• If diarrhea persists despite PPI therapy, this confirms that upper GI pathology is not the primary cause and mandates completion of small bowel evaluation 3
• Repeat endoscopy at 8 weeks if symptoms do not improve to assess healing and obtain biopsies if not previously done 1

Long-term Management:

• Once diagnosis is established, tailor therapy to the specific underlying condition 3
• If all investigations remain negative, consider functional bowel disorder only after excluding organic disease comprehensively 3
• Maintenance PPI therapy (omeprazole 20 mg daily) may be required for esophagitis and gastritis, though dosage can be reduced once healing is confirmed 1

Key Clinical Pearls

The combination of hematin findings and chronic progressive diarrhea represents two distinct pathologic processes that must both be addressed: 2, 3

• Hematin indicates severe gastric hyperacidity requiring PPI therapy 2
• Chronic nocturnal diarrhea indicates small bowel or colonic pathology requiring specific diagnosis 3
• Do not assume the upper GI findings explain the diarrhea - this is a common diagnostic error 3

Histological evaluation is essential as endoscopic appearance correlates poorly with histologic findings in gastroduodenitis, with only 56% agreement between endoscopic and histologic diagnoses in the stomach 4