Gallstone disease differential diagnosis

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

Overview

Gallstone disease must be differentiated from other diseases that cause epigastric, and left and right hypochondriac pain (right upper quadrant) such as: Abdominal pain, esophageal chest pain,gastroesophageal reflux disorder, peptic ulcer disease, non-ulcer dyspepsia,hepatitis, functional gallbladder disorder, sphincter of Oddi dysfunction,appendicitis, bile duct stricture, chronic pancreatitis, irritable bowel syndrome, ischemic heart disease, pyelonephritis, ureteral calculi and complications of gallstone disease include: acute cholecystitis, choledocholithiasis, acute pancreatitis, and acute cholangitis.

Differentiating Gallstone disease from other Diseases

As Gallstone disease manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. The presence of biliary colic is an important diagnostic feature to distinguish between gallstones and non-biliary disorders. It has been shown that this feature is predictive of finding stones on imaging. However, it is important to note that biliary colic concomitant in patients with other biliary disorders such as acute cholecystitis, choledocholithiasis, sphincter of Oddi dysfunction, and functional gallbladder disorder.

Laboratory studies can be helpful, along side clinical presentation in making a preliminary diagnosis:

• Liver biochemical tests (serum aminotransferases, total bilirubin, alkaline phosphatase), which may be abnormal in patients with hepatitis, biliary tract obstruction, or (less commonly) acute cholecystitis
• Serum amylase and lipase, which are elevated in acute pancreatitis
• Complete blood count, which may show an elevated white blood cell count in patients with acute cholecystitis or acute cholangitis
• Urine analysis, which may show indicate a urinary tract infection or ureteral calculi

Other tests that may be indicated depending upon the patient's symptoms and history including:

• Upper endoscopy to look for peptic ulcer disease
• Endoscopic ultrasonography to look for chronic pancreatitis
• Endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry to look for sphincter of Oddi dysfunction
• Cholescintigraphy with or without cholecystokinin (CCK)-stimulation to look for acute cholecystitis and functional gallbladder disorder, respectively
• Testing for ischemic heart disease
• Esophageal manometry to look for esophageal sources of chest pain, such as esophageal spasm

To review a table of differential diagnoses for disease symptoms including jaundice, abdominal pain and fever, please click here:

Differential 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

Classification of pain in the abdomen based on etiology Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Jaundice Diarrhea GI Bleed Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Abdominal causes Inflammatory causes Pancreato-biliary disorders Acute suppurative cholangitis RUQ + + + − − + + + N Abnormal LFT WBC >10,000 Ultrasound shows biliary dilatation/stents/tumor Septic shock occurs with features of SIRS Acute cholangitis RUQ + − + − − − − − N Abnormal LFT Ultrasound shows biliary dilatation/stents/tumor Biliary drainage (ERCP) + IV antibiotics Acute cholecystitis RUQ + − + − − − − − Hypoactive Hyperbilirubinemia Leukocytosis Ultrasound shows gallstone and evidence of inflammation Murphy’s sign Acute pancreatitis Epigastric + − ± − − ± + + N Increased amylase / lipase Ultrasound shows evidence of inflammation CT scan shows severity of pancreatitis Pain radiation to back Chronic pancreatitis Epigastric − − ± + − − − − N Increased amylase / lipase Stool fat content Pancreatic function test CT scan Calcification Pseudocyst Dilation of main pancreatic duct Predisposes to pancreatic cancer Pancreatic carcinoma Epigastric - - + + - - - - N ↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9  MDCT with  PET/CT MRI Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau's syndrome) Pancreatic panniculitis Primary biliary cirrhosis RUQ/Epigastric − − + − + in late presentation − − − N Increased AMA level, abnormal LFTs Primary sclerosing cholangitis RUQ + − + − − − − − N Increased liver enzymes Increased IgM, IgG4 Anti-neutrophil cytoplasmic antibody (p-ANCA) Anti-nuclear antibody (ANA) Anti-smooth muscle antibody (Anti-Sm) Anti-endothelial antibody Anti-cardiolipin antibody ERCP and MRCP shows Multiple segmental strictures Mural irregularities Biliary dilatation and diverticula Distortion of biliary tree The risk of cholangiocarcinoma in patients with primary sclerosing cholangitis is 400 times higher than the risk in the general population. Cholelithiasis RUQ/Epigastric ± − ± − − − − − N to hyperactive for dislodged stone Leukocytosis Ultrasound shows gallstone Fatty food intolerance Gastric causes Peptic ulcer disease Diffuse ± − − − Gastric ulcer- melena and hematemesis Duodenal ulcer- melena and hematochezia + in 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 ± − − − + in chronic gastritis − − − N H.pylori infection diagnostic tests Endoscopy H.pylori gastritis guideline recommendation Gastroesophageal reflux disease Epigastric − − − − − − − − N Esophageal manometry Gastric emptying studies Endoscopy for alarm signs Gastric outlet obstruction Epigastric − − − − − − − − Hyperactive Complete blood count Basic metabolic panel Abdominal x-ray- air fluid level Barium upper GI studies- narrowed pylorus Succussion splash Gastroparesis Epigastric - - - - - ± - - Hyperactive/hypoactive Hemoglobin Fasting plasma glucose Serum total protein, albumin, thyrotropin (TSH), and an antinuclear antibody (ANA) titer HbA1c Scintigraphic gastric emptying Succussion splash Single photon emission computed tomography (SPECT) Full thickness gastric and small intestinal biopsy Gastrointestinal perforation Diffuse + ± ± − +, depends on site + + ± Hyperactive/hypoactive WBC> 10,000 Air under diaphragm in upright CXR Hamman's sign Dumping syndrome Lower and then diffuse − − − + − + − − Hyperactive Glucose challenge test Hydrogen breath test Upper GI series Gastric emptying study Postgastrectomy Intestinal causes Acute appendicitis Starts in epigastrium, migrates to RLQ + +in pyogenic appendicitis − − − + in perforated appendicitis + + Hypoactive Leukocytosis Ultrasound shows evidence of inflammation Nausea & vomiting, decreased appetite Acute diverticulitis LLQ + ± − ± Hematochezia + in perforated diverticulitis + + Hypoactive Leukocytosis CT scan and ultrasound shows evidence of inflammation History of constipation Inflammatory bowel disease Diffuse ± − ± ± Hematochezia − − − N/ 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 Irritable bowel syndrome Diffuse ± − − + − − − − N Tests done to exclude other diseases as it diagnosis of exclusion Tests done to exclude other diseases as it diagnosis of exclusion Symptomatic treatment High dietary fiber Osmotic laxatives Antispasmodic drugs Whipple's disease Diffuse ± − ± + − ± − − N Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites Toxic megacolon Diffuse + − − + − + ± − Hypoactive Anemia Leukocytosis especially in patients with Clostridium difficile infection Hypoalbuminemia Metabolic alkalosis associated with a poor prognosis Metabolic acidosis secondary to ischemic colitis CT scan shows: Dilated transverse colon Loss of colonic haustrations Segmental parietal thinning Intraluminal soft-tissue masses Ultrasound shows: Loss of haustra coli of the colon Hypoechoic and thickened bowel walls with irregular internal margins in the sigmoid and descending colon Prominent dilation of the transverse colon (>6 cm) Insignificant dilation of ileal bowel loops (diameter >18 mm) with increased intraluminal gas and fluid Tropical sprue Diffuse + − − + − − − − N Fat soluble vitamin deficiency Hypoalbuminemia Fecal stool test Barium studies show dilation and edema of mucosal folds Steatorrhea- 10-40 g/day (Normal=5 g/day) Celiac disease Diffuse − − − + − − − − Hyperactive IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Small bowel biopsy USG Bull’s eye or target pattern Pseudokidney sign Gluten allergy Infective colitis Diffuse + − − + Hematochezia + 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 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 Hepatic causes Viral hepatitis RUQ + − + + in Hep A and E − + in fulminant hepatitis +in acute + N Abnormal LFTs Viral serology USG Hep A and E have fecoral route of transmission and Hep B and C transmits via blood transfusion and sexual contact. Liver masses RUQ + + in Liver abscess ± − + in Hepatocellular carcinoma + in sepsis + in Liver abscess + in Liver abscess N CBC LFTs USG Liver abscess RUQ + + + ± - + + ± Normal/hypoactive CBC Blood cultures Abnormal liver function tests US CT Hepatocellular carcinoma/Metastasis RUQ + - + - - - - - Normal Hyperactive if obstruction present High levels of AFP in serum Abnormal liver function tests US CT Liver biopsy Other symptoms: Splenomegaly Variceal bleeding Ascites Spider nevi Asterixis Budd-Chiari syndrome RUQ ± − ± − + 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 − − − − + 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 − − + − varices + − − N Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia USG Nodular, shrunken liver Ascites Stigmata of liver disease Cruveilhier- Baumgarten murmur Peritoneal causes Spontaneous bacterial peritonitis Diffuse + + + in cirrhotic patients + − ± + + Hypoactive Ascitic fluid PMN>250 cells/mm³ Culture: Positive for single organism Ultrasound for evaluation of liver cirrhosis Renal causes Pyelonephritis Lumbar region + ± - - - + ± ± Hypoactive Urinalysis Urine culture Blood culture CT MRI Renal punch positive Renal colic Flank pain − − − − − − − − N Hematuria CT scan and ultrasound Colicky abdominal pain Dysuria Hollow Viscous Obstruction Small intestine obstruction Diffuse + − − − − + + ± Hyperactive then absent Leukocytosis with left shift indicates complications Abdominal X ray dilated loops of bowel with air fluid levels gasless abdonen "Target sign"– , indicative of intussusception Venous cut-off sign" – suggests thrombosis Volvulus Diffuse +in perforated cases − − − − +in perforated cases + + Hyperactive then absent Leukocytosis CT scan and abdominal X ray U shaped sigmoid colon "Whirl sign" Biliary colic RUQ − − + − − − − − N Increased bilirubin and alkaline phosphatase Ultrasound Nausea & vomiting Vascular Disorders Ischemic causes Mesenteric ischemia Periumbilical + if bowel becomes gangrenous − − + Hematochezia + if bowel becomes gangrenous + 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, worsens with eating Acute ischemic colitis Diffuse + ± − + Massive + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel Can lead to shock Hemorrhagic causes Ruptured abdominal aortic aneurysm Diffuse ± − − − Herald to massive + − − N Fibrinogen D-dimer Focused Assessment with Sonography in Trauma (FAST)  Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage Diffuse ± − − − Massive + − − N Anemia CT scan History of trauma Gynaecological Causes Tubal causes Torsion of the cyst RLQ / LLQ − − − − − − ± ± N Increased ESR and CRP Ultrasound Sudden onset & severe pain with nausea and vomiting Acute salpingitis RLQ / LLQ + ± − − − − ± ± N Leukocytosis Pelvic ultrasound Vaginal discharge Cyst rupture RLQ / LLQ − − − − − + ± ± N Increased ESR and CRP Ultrasound Sudden onset sever pain with nausea and vomiting Pregnancy Ruptured ectopic pregnancy RLQ / LLQ − − − − − + + + N Positive pregnancy test Ultrasound History of missed period and vaginal bleeding Extra-abdominal causes Pulmonary disorders Pleural empyema RUQ/Epigastric + ± − − − − − − N Thoracentesis Chest X-ray Pleural opacity USG Localization of effusion Physical examination Crackles Egophony Increased tactile fremitus Pulmonary embolism RUQ/LUQ ± - - - - ± - - N ABGs D-dimer CXR V/Q scan Spiral CT pulmonary angiogram Pneumonia RUQ/LUQ + + - - - + - - N/Hypoactive ABGs Eosinophilia Pancytopenia CXR CT chest Bronchoscopy Cardiovascular disorders Myocardial Infarction Epigastric − − − − − + in cardiogenic shock − − N ECG Cardiac enzymes Echocardiogram Wall motion abnormality Wall rupture Septal rupture Complications: Arrythmias Mitral regurgitation Ventricular wall rupture Septal rupture

References

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