Upper gastrointestinal bleeding differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The various causes responsible for UGIB include peptic ulcer disease, esophagitis, gastritis/gastropathy, esophagogastric varices, ectopic varices, portal hypertensive gastropathy, angiodysplasia, dieulafoy's lesion, gastric antral vascular ectasia, Mallory-Weiss syndrome and upper GI tumors and must be differentiated from one another.

Differentiating Upper Gastrointestinal Bleeding from other Diseases

Several diseases can present with UGIB, and hence must be differentiated from one another.

The following table summarizes the various causes of Upper gastrointestinal bleeding

Disease/Cause	Bleeding manifestations				Symptoms				Risk factors	Endoscopic findings
	Hematemesis	Melena	Hematochezia	Occult blood	Abdominal pain	Dysphagia	Dyspepsia	Weighloss
Ulcerative or erosive
Peptic ulcer disease	+	+	+	+	+	-	+	+/-	NSAIDs Infections: Helicobacter pylori CMV HSV Stress ulcer ZES	Ulcer with smooth, regular, rounded edges Ulcer base often filled with exudate Examination of the ulcer may reveal: Active bleeding Nonbleeding visible vessel Adherent clot Flat pigmented spot Clean ulcer base
Esophagitis	+	+	-	+	-	+	-	-	Gastroesophageal reflux disease Medications: Tetracycline Doxycycline Clindamycin Trimethoprim-sulfamethoxazole NSAIDs Bisphosphonates Potassium chloride Quinidine Iron supplements  Infections: HSV CMV Candida albicans HIV	Peptic esophagitis The ulcerations are usually irregularly shaped or linear, multiple, and distal. Pill-induced Ulcerations are usually singular and deep, occurring at points of stasis (especially near the carina), with sparing of the distal esophagus Infectious esophagitis: HSV – Discrete, superficial ulcers, with well-demarcated borders that tend to involve the upper or mid-esophagus; vesicles may be seen CMV – Ulcers range from small and shallow to large (>1 cm) and deep; most patients have multiple lesions Candida – Diffuse white plaques HIV – Tends to involve the mid to distal esophagus, ulcers may be shallow or deep, and may be large
Gastritis/gastropathy	+	+	-	+	+	-	+	-	Risk factors: H. pylori NSAIDs Excessive alcohol consumption Radiation injury Physiologic stress Weight loss surgery Bile reflux Risk factors for bleeding: Anticoagulant use	Erythematous mucosa Superficial erosions Nodularity Diffuse oozing
Complications of portal hypertension
Esophagogastric varices	+	+	+	-	+	-	-	-	Portal hypertension from: Cirrhosis Portal vein thrombosis	Vascular structures that protrude into the esophageal and/or gastric lumen Findings associated with an increased risk of hemorrhage: Longitudinal red streaks on the varices (red wale marks) Cherry-colored spots that are flat and overlie varices Raised, discrete red spots
Ectopic varices	+	+	+	-	-	-	-	-		Vascular structures that protrude into areas of the gastrointestinal tract lumen other than the esophagus or stomach (eg, small bowel, rectum)
Portal hypertensive gastropathy	+	+	+	+	+	-	-	-		Mosaic-like pattern that gives the gastric mucosa a "snakeskin" appearance
Vascular lesions
Angiodysplasia	+	+	+	+	-	-	-	-	End-stage renal disease Aortic stenosis Hereditary hemorrhagic telangiectasia Von Willebrand disease Radiation therapy	Small (5 to 10 mm), flat, cherry-red lesions, often with a fern-like pattern of arborizing, ectatic blood vessels radiating from a central vessel.
Dieulafoy's lesion	+	+	+	-	+	-	-	-	Bleeding may be associated with NSAIDs use Hypertension Chronic kidney disease Diabetes Alcohol abuse	Usually located in the proximal stomach May have active arterial spurting from the mucosa without an associated ulcer or mass If the bleeding has stopped, there may be a raised nipple or visible vessel without an associated ulcer
Gastric antral vascular ectasia	+	+	+	+	+	-	-	-	Cirrhosis with portal hypertension Chronic kidney disease Diabetes mellitus Scleroderma Bone marrow transplantation	Longitudinal rows of flat, reddish stripes radiating from the pylorus into the antrum.
Traumatic or iatrogenic
Mallory-Weiss syndrome	+	+	+	-	-	-	-	-	Vomiting/retching (often related to alcohol consumption) Straining at stool or lifting Coughing Seizures Blunt abdominal trauma Hiatal hernia	Tear in the esophagogastric junction. Usually singular and longitudinal, but may be multiple. The tear may be covered by an adherent clot.
Foreign body ingestion	+	+	+	+	-	+	-	-	Psychiatric disorders Dementia Loose dentures	Visualization of the foreign body endoscopically.
Post-surgical anastomotic hemorrhage (marginal ulcers)	+	+	+	+	+	-	+	-	Gastric bypass surgery NSAID use H. pylori infection Smoking	Ulceration/friable mucosa at an anastomotic site.
Aortoenteric fistula	+	+	+	-	+	-	-	-	Infectious aortitis Prosthetic aortic graft Atherosclerotic aortic aneurysm Penetrating ulcers Tumor invasion Trauma Radiation injury Foreign body perforation	Endoscopy may reveal a graft, an ulcer or erosion at the site Adherent clot, or an extrinsic pulsatile mass in the distal duodenum or esophagus.
Tumors
Upper GI tumors	+	+	+	+	+	+	+	+	History of alcoholism, smoking	Ulcerated mass in the esophagus, stomach, or duodenum. In gastric malignancies: The folds surrounding the ulcer crater may be nodular, clubbed, fused, or stop short of the ulcer margin The margins may be overhanging, irregular, or thickened Bleeding lymphoma may appear as An ulcerated mass Polypoid lesion As a gastric ulcer
Miscellaneous
Hemobilia	+	+	+	-	+	-	-	-	History of: Cholecystectomy Endoscopic biliary biopsies or stenting TIPS placement Angioembolization Blunt or penetrating abdominal trauma Gallstones Cholecystitis Hepatic or bile duct tumors Intrahepatic stents Hepatic artery aneurysms Hepatic abscesses	Blood or clot emanating from the ampulla. ERCP may reveal a filling defect in the bile duct
Hemosuccus pancreaticus	+	+	+	-	+	-	+	-	Chronic pancreatitis Pancreatic pseudocysts Pancreatic tumors Pancreatic pseudoaneurysm Therapeutic endoscopy of the pancreas or pancreatic duct: Pancreatic stone removal Pancreatic duct sphincterotomy Pseudocyst drainage Pancreatic duct stenting	Blood or clot emanating from the ampulla. Cross-sectional imaging or angiography is often required to confirm the diagnosis.

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Peptic ulcer disease Diffuse ± − + − − − + Gastric ulcer- melena and hematemesis Duodenal ulcer- melena and hematochezia Positive if perforated Positive if perforated Positive if perforated N Ascitic fluid LDH > serum LDH Glucose < 50mg/dl Total protein > 1g/dl Air under diaphragm in upright CXR Upper GI endoscopy for diagnosis Gastritis Epigastric ± − + − − − Positive in chronic gastritis + − − − N H.pylori infection diagnostic tests Endoscopy H.pylori gastritis guideline recommendation Gastrointestinal perforation Diffuse + ± - ± − − − + + + ± Hyperactive/hypoactive WBC> 10,000 Air under diaphragm in upright CXR Hamman's sign Acute diverticulitis LLQ + ± + − + ± − + Positive in perforated diverticulitis + + Hypoactive Leukocytosis CT scan Ultrasound History of constipation Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease String sign on abdominal x-ray in Crohn's disease Extra intestinal findings: Uveitis Arthritis Infective colitis Diffuse + − ± − − + − + Positive in fulminant colitis ± ± Hyperactive Stool culture and studies Shiga toxin in bloody diarrhea PCR CT scan Bowel wall thickening Edema Colon carcinoma Diffuse/localized − − − − ± ± + + ± − − Normal or hyperactive if obstruction present CBC Carcinoembryonic antigen (CEA) Colonoscopy Flexible sigmoidoscopy Barium enema CT colonography  PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Budd-Chiari syndrome RUQ ± − − ± − − − Positive in liver failure leading to varices − − − N Elevated serum aspartate aminotransferase and alanine aminotransferase levels may be more than five times the upper limit of the normal range. Elevated serum alkaline phosphatase and bilirubin levels, decreased serum albumin level. Findings on CT scan suggestive of Budd-Chiari syndrome include: Early enhancement of the caudate lobe and central liver around the inferior vena cava Delayed enhancement of the peripheral liver with accompanying central low density (flip-flop appearance) Peripheral zones of the liver show reversed portal venous blood flow In the chronic phase, there is caudate lobe enlargement and atrophy of the peripheral liver in affected areas Ascitic fluid examination shows: Total protein more than 2.5 g per deciliter White blood cells are usually less than 500/μL. Hemochromatosis RUQ − − − − − − − Positive in cirrhotic patients − − − N >60% TS >240 μg/L SF Raised LFT Hyperglycemia Ultrasound shows evidence of cirrhosis Extra intestinal findings: Hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections Cirrhosis RUQ − − − + − − + + + − − N Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia US Nodular, shrunken liver Ascites Stigmata of liver disease Cruveilhier- Baumgarten murmur Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock Ruptured abdominal aortic aneurysm Diffuse ± − + − − − + + + − − N Fibrinogen D-dimer Focused Assessment with Sonography in Trauma (FAST)  Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage Diffuse ± − ± − − − − + + − − N ↓ Hb ↓ Hct CT scan History of trauma

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