Occult blood in stool d/d
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Occult Blood in Stool - Differential Diagnosis
Occult GI bleeding is defined as a positive fecal occult blood test (FOBT/FIT) or iron-deficiency anemia without visible blood in the stool. Unlike overt GI bleeding (hematemesis, melena, hematochezia), there is no blood visible to the naked eye. The differential spans the entire GI tract.
- Washington Manual of Medical Therapeutics, p. 663
- Harrison's Principles of Internal Medicine 22E, p. 362-363
Classification by Anatomical Location
UPPER GI TRACT (proximal to Ligament of Treitz)
FOBT tests detect hemoglobin/heme and are sensitive for colonic blood loss, but will also detect larger amounts of upper GI bleeding.
| Cause | Notes |
|---|---|
| Peptic ulcer disease (gastric/duodenal) | Most common cause of upper GI bleeding overall; chronic low-level loss causes occult positivity; H. pylori and NSAIDs are key drivers |
| Erosive gastritis / esophagitis | NSAIDs, alcohol, aspirin - chronic mucosal erosions |
| Esophageal/gastric varices | Portal hypertension; more often overt but can be occult |
| Mallory-Weiss tear | Usually after retching; typically overt but may be occult |
| Angiodysplasia (upper GI) | Vascular ectasias; important cause of chronic occult loss |
| Dieulafoy lesion | Tortuous submucosal arteriole, classically in gastric fundus |
| Gastric cancer / esophageal cancer | Malignancy - occult loss is a classic presentation |
| Gastric antral vascular ectasia (GAVE) | "Watermelon stomach"; causes chronic occult or overt bleeding |
| Celiac disease / sprue | Poor iron absorption + mucosal bleeding; occult loss with IDA |
SMALL INTESTINE
The small bowel is the source in up to 5% of all GI bleeds and should be suspected when EGD + colonoscopy are both unrevealing. Capsule endoscopy detects a source in 50-70% of suspected small intestinal bleeding cases, with mucosal vascular ectasia being the most common finding.
| Cause | Notes |
|---|---|
| Angiodysplasia (small bowel) | Most common small bowel occult bleed source |
| Meckel's diverticulum | Ectopic gastric mucosa causes peptic ulceration of adjacent small intestinal mucosa; presents with occult bleeding or pain (younger patients) |
| Crohn's disease | Transmural inflammation; chronic blood loss |
| Small bowel tumors | GIST, lymphoma, carcinoid, adenocarcinoma |
| Small bowel ulcers | NSAID-induced, radiation-induced |
| Aortoenteric fistula | After aortic surgery; herald bleeds |
LOWER GI TRACT (colon and rectum)
Colonoscopy is the primary diagnostic tool for occult blood, especially age >50 or with family history of colorectal neoplasia.
| Cause | Notes |
|---|---|
| Colorectal cancer | Most important cause to exclude; FOB screening programs are designed for this |
| Colorectal adenomatous polyps | ~30% of patients with occult blood + IDA will have polyps or cancer on colonoscopy |
| Colonic angiodysplasia | Especially right colon; elderly patients; commonest cause of chronic obscure lower GI bleed |
| Diverticulosis | Chronic/occult bleeding is uncommon (usually causes abrupt painless overt bleed) |
| Inflammatory bowel disease | Ulcerative colitis, Crohn's colitis |
| Infectious colitis | Salmonella, Shigella, Campylobacter, E. coli O157:H7, C. difficile |
| Ischemic colitis | Splenic flexure / descending colon watershed zones |
| Radiation proctocolitis | Post-pelvic radiotherapy |
| Solitary rectal ulcer syndrome |
ANORECTAL (usually overt, but can cause positive FOBT)
| Cause | Notes |
|---|---|
| Hemorrhoids (internal) | Coating of stool; may cause FOBT positivity |
| Anal fissure | Usually overt but can be subtle |
| Rectal cancer / polyp | Must be excluded even with "obvious" hemorrhoids |
Non-GI Causes of False-Positive FOBT
Guaiac-based tests (but not immunochemical FIT tests) can give false positives from:
- Dietary: Red meat, uncooked vegetables (peroxidases - broccoli, turnips, horseradish)
- Medications: NSAIDs, aspirin, iron supplements, steroids, alcohol
- Vitamin C: High doses cause false negatives (not false positives)
- Upper respiratory / oral bleeding: Swallowed blood from epistaxis, gum disease
- Menstrual blood contamination
The newer FIT (fecal immunochemical test) uses antibodies specific to human hemoglobin and is not affected by dietary peroxidases - it is now preferred for colorectal cancer screening.
- Tietz Textbook of Laboratory Medicine 7th Edition, p. 138
Important Clinical Pearls
- Iron-deficiency anemia in men and postmenopausal women should always prompt investigation for occult GI blood loss; colonoscopy is indicated even in the absence of detectable FOBT positivity
- ~30% of such patients will have large colonic polyps or colorectal cancer
- If colonoscopy is unrevealing, upper GI endoscopy should follow; if that is negative, duodenal biopsies should be obtained (to exclude celiac sprue)
- If both EGD and colonoscopy are negative: capsule endoscopy, CT/MR enterography, or deep enteroscopy for the small bowel
- Patients with positive FOBT should undergo colonoscopy, especially if >50 years or with family history of colonic neoplasia
Summary Framework
Occult Blood in Stool
├── UPPER GI (proximal to Ligament of Treitz)
│ ├── Peptic ulcer disease ← most common upper GI cause
│ ├── Erosive gastritis / esophagitis
│ ├── Varices, Mallory-Weiss, Dieulafoy
│ ├── Angiodysplasia / GAVE
│ └── Malignancy (gastric, esophageal)
│
├── SMALL BOWEL
│ ├── Angiodysplasia ← most common small bowel cause
│ ├── Meckel's diverticulum
│ ├── Crohn's disease
│ └── Tumors (GIST, lymphoma, carcinoid)
│
├── COLON
│ ├── Colorectal cancer / polyps ← most important to exclude
│ ├── Angiodysplasia (right colon)
│ ├── IBD, infectious/ischemic colitis
│ └── Diverticulosis (less commonly occult)
│
├── ANORECTUM
│ ├── Hemorrhoids, anal fissure
│ └── Rectal cancer
│
└── FALSE POSITIVES (guaiac only)
├── Red meat, vegetable peroxidases
├── NSAIDs, aspirin, alcohol
└── Swallowed blood (epistaxis)
Sources: Harrison's Principles of Internal Medicine 22E, p. 362-365; Washington Manual of Medical Therapeutics, p. 663; Symptom to Diagnosis: An Evidence-Based Guide 4th Ed., p. 354; Tietz Textbook of Laboratory Medicine 7th Ed., p. 138
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