Is an upper endoscopy recommended for chronic diarrhea of unknown origin?

Upper Endoscopy for Chronic Diarrhea of Unknown Origin

Upper endoscopy is NOT routinely recommended for chronic diarrhea of unknown origin; colonoscopy with ileoscopy and multiple biopsies is the cornerstone investigation, with upper endoscopy reserved specifically for cases where clinical features suggest small bowel malabsorption. 1, 2

Primary Diagnostic Approach

The British Society of Gastroenterology explicitly states that colonoscopy with ileoscopy and biopsy is the preferred investigation for chronic diarrhea of uncertain origin, yielding a diagnosis in approximately 15-20% of cases, and up to 40% when inflammatory bowel disease is suspected. 1, 2 This is because:

• Most pathology causing chronic diarrhea originates in the colon and terminal ileum, including microscopic colitis (15% of cases), inflammatory bowel disease, and neoplasia. 1, 2
• Routine ileoscopy increases diagnostic yield to 18% in non-HIV patients and 36% in suspected IBD cases with normal colonoscopy. 1, 2
• Multiple biopsies from both right and left colon are mandatory even when mucosa appears normal, as microscopic colitis has entirely normal-appearing mucosa endoscopically but shows characteristic histologic changes. 1, 3

When Upper Endoscopy IS Indicated

Upper endoscopy with distal duodenal biopsies should be performed in these specific clinical scenarios:

Clinical Features Suggesting Malabsorption

• Weight loss, steatorrhea (bulky, pale, malodorous stools), or nutritional deficiencies suggest small bowel malabsorption requiring upper endoscopy. 1, 2
• Negative celiac serology but persistent clinical suspicion for celiac disease or other small bowel enteropathies warrants duodenal biopsies. 1, 2
• Symptoms of upper GI disease including dyspepsia or upper abdominal pain in the context of chronic diarrhea. 2

Specific Patient Populations

• Pediatric IBD patients require upper endoscopy for accurate disease classification and to differentiate Crohn's disease from ulcerative colitis. 2
• HIV-positive patients with chronic diarrhea may benefit from upper endoscopy to jejunum to detect microsporidiosis (found in 7 patients) and cryptosporidiosis (found in 2 patients) when colonoscopy is unrevealing. 4

Critical Evidence Gaps and Limitations

The diagnostic yield of upper endoscopy in unselected chronic diarrhea patients is poorly documented and likely low. 1, 2 The British Society of Gastroenterology states: "There is little information on the diagnostic yield of upper GI endoscopy in patients whose diarrhoea is suspected to be due to malabsorption." 1

In a study of chronic diarrhea patients, upper endoscopy revealed mucosal abnormalities in only 37.5% (3/8) of cases, compared to colonoscopy's much higher yield. 5 Another study comparing upper versus lower endoscopy found that lower endoscopy yielded relevant diagnoses more often than upper endoscopy in patients with negative stool examinations. 6

Algorithmic Approach

Step 1: Perform colonoscopy with ileoscopy first in all patients with chronic diarrhea of unknown origin, obtaining multiple biopsies from six segments including normal-appearing mucosa. 1, 2, 3

Step 2: Consider upper endoscopy ONLY if:

• Clinical features suggest malabsorption (weight loss, steatorrhea, nutritional deficiencies) 1, 2
• Celiac serology is negative but clinical suspicion remains high 1, 2
• Patient is HIV-positive with negative colonoscopy 4
• Patient is pediatric with suspected IBD 2
• Upper GI symptoms coexist with diarrhea 2

Step 3: If both endoscopies are negative, consider video capsule endoscopy, which showed a 42.9% diagnostic yield in chronic diarrhea patients, particularly identifying Crohn's disease (19.8% of cases). 7

Common Pitfalls to Avoid

• Do not perform upper endoscopy routinely without specific clinical indicators of malabsorption, as this increases cost and procedural burden without improving diagnostic yield. 1, 2
• Do not skip colonoscopy in favor of upper endoscopy, as nearly half of neoplastic lesions occur proximal to the splenic flexure and microscopic colitis requires colonic biopsies for diagnosis. 1, 2
• Do not rely on endoscopic appearance alone—obtain biopsies even from normal-appearing mucosa, as microscopic colitis and early IBD may have normal endoscopic findings. 1, 3
• Do not forget to perform ileoscopy during colonoscopy, as 36% of patients with normal colonoscopy and diarrhea had terminal ileal disease. 1