Irritable bowel syndrome differential diagnosis

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

Overview

Irritable bowel syndrome must be differentiated from other diseases that cause diarrhea, constipation, and abdominal pain, such as Celiac disease, Inflammatory bowel disease(Crohn's disease and Ulcerative colitis) Thyroid disease (Hyper or Hypothyroidism), strictures due to ischemia, diverticulitis or ischemia, among others.

The differential diagnosis for Irritable bowel syndrome can be listed based on predominant symptoms, such as constipation predominant, diarrhea predominant and pain predominant diseases.

Differentiating Irritable Bowel Syndrome from other Diseases

Diseases with similar symptoms

• Celiac disease
• Crohn's disease
• Zollinger-Ellison syndrome
• VIPoma
• Diverticulitis
• Endometriosis
• Gallstones
• Gastroesophageal reflux disease (GERD)
• Inflammatory bowel disease
• Lactose intolerance
• Thyroid disease- Hyperthyroidism/Hypothyroidism
• Chronic pancreatitis
• Small bacterial overgrowth
• Intermittent small bowel obstruction

Differential diagnosis of abdominal pain

The differential diagnosis of IBS based on abdominal pain is as follows:

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

Classification of pain in the abdomen based on etiology Disease Clinical manifestations Diagnosis Comments Symptoms Signs Fever Rigors and chills Abdominal Pain Jaundice Diarrhea Melena/ hematochezia/ hemtemesis 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 Pain radiation to back Primary biliary cirrhosis − − RUQ/Epigastric + − − − − − 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 Murphy’s sign 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 − Gastroesophageal reflux disease − − Epigastric − − − − − − Gastric outlet obstruction − − Epigastric − − − ± Hyperactive Gastrointestinal perforation + ± Diffuse ± − +, depends on site + + ± WBC> 10,000 Air under diaphragm in upright CXR Dumping syndrome − − Lower and then diffuse Intestinal causes Acute appendicitis + +in pyogenic appendicitis Starts in epigastrium, migrates to RLQ − − − + in perforated appendicitis + + Hypoactive Leukocytosis Ultrasound shows evidence of inflammation Nausea & vomiting, decreased appetite Acute diverticulitis + ± LLQ − − Hematochezia − + − Hypoactive Leukocytosis CT scan and ultrasound shows evidence of inflammation Inflammatory bowel disease ± − Diffuse ± Hematochezia 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 + − Celiac disease − − Diffuse ±, also dermatitis herpetiformis + − − − − Hyperactive (increased sounds) IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Infective colitis + Hepatic causes Viral hepatitis + − RUQ + − − − + Liver masses + + in Liver abscess RUQ ± − − + in sepsis 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 Dull / aching + with infections and GI involvement − + in cirrhotic patients may be in cardicmyopathy − − >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 − 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 Hollow Viscous Obstruction Small intestine obstruction − − Diffuse − − − − + ± Hyperactive then absent Leukocytosis Abdominal X ray Nausea & vomiting associated with constipation, abdominal distention Volvulus − − Diffuse − − − − + − Hypoactive Leukocytosis CT scan and abdominal X ray Nausea & vomiting associated with constipation, abdominal distention Biliary colic − − RUQ + − − − − − N Increased bilirubin and alkaline phosphatase Ultrasound Nausea & vomiting Renal colic − − Flank pain − − − − − − N Hematuria CT scan and ultrasound Colicky abdominal pain associated with nausea & vomiting Vascular Disorders Ischemic causes Mesenteric ischemia ± − Periumbilical − + Hematochezia ± − − Hyperactive Leukocytosis and lactic acidosis CT scan Nausea & vomiting, normal physical examination Acute ischemic colitis ± ± Diffuse − + Massive + + Hyperactive then absent Leukocytosis CT scan Nausea & vomiting Hemorrhagic causes Ruptured abdominal aortic aneurysm − − Diffuse − − Massive + − − N Normal CT scan 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 sever 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 Cardiovascular disorders Myocardial Infarction − − Epigastric − − − + in cardiogenic shock − − N

Differential Diagnosis of Irritable bowel syndrome on the basis of abdominal pain and diarrhea:

Diarrhea with abdominal pain/cramping may be caused by infectious diseases, celiac disease, parasites, food allergies and lactose intolerance. See the list of causes of diarrhea for other conditions which can cause diarrhea. Celiac disease in particular is most often misdiagnosed as IBS. The differential diagnosis of irritable bowel syndrome based on abdominal pain and diarrhea is as follows:

Cause			Osmotic gap		History	Physical exam	Gold standard	Treatment
			< 50 mOsm per kg	> 50 mOsm per kg*
Watery	Secretory	Crohns	+	-	Abdominal pain followed by diarrhea	Abdominal tenderness when palpated in severe disease Blood seen on rectal exam Fever Tachycardia Hypotension	Colonoscopy with biopsy	Topical mucosamine and corticosteroids are preferred Mesalamineand sulfasalazine are used for remission
		Zollinger-Ellison syndrome	+	-	Abdominal pain and diarrhea Dyspepsia Upper or lower gastrointestinal bleeding	Abdominaltenderness whenpalpated in severe disease Blood seen on rectal exam, Hematochezia Hematemesis Tachycardia Hypotension	Gastrin levels	Proton pump inhibitors Octreotide
		Hyperthyroidism	+	-	Abdominal pain and diarrhea Dyspepsia Upper or lower gastrointestinal bleeding	Lump in the neck Proptosis Tremors Increased DTR	TSH with T3 and T4	Carbimazole and methimazole Beta blockers like propylthiouracil Iodine-131
		VIPoma	+	-	Watery diarrhea Dehydration(thirst, dry skin, dry mouth, tiredness, headaches, and dizziness) Lethargy, muscle weakness Nausea, vomiting Crampy abdominal pain Weight loss Flushing	Lump in the neck Proptosis Tremors Increased DTR	Elevated VIPlevels Followed by imaging	Sandostatin or chemotherapy for malignant tumors Surgical removal of the tumor
	Osmotic	Lactose intolerance	-	+	Abdominal pain Bloating Diarrhea Flatulence	Abdominal tenderness	Intestinal biopsy	Avoidance of dietary lactose Substitution to maintain nutrient intake Regulation of calcium intake Use of enzymelactase
		Celiac disease	-	+	May be asymptomatic Vague abdominal pain Diarrhea Weight loss Malabsorption/ steatorrhea Bloating	Abdominal pain and cramping Abdominal distention Tetany Mouth ulcers Dermatitis herpetiformis Signs of the fat-soluble vitamins A, D, E, and K deficiency	IgA tissue transglutaminase antibody	Gluten-free diet
	Functional	Irritable bowel syndrome	-	-	Abdominal pain or discomfort recurring at least 3 days per month in the past 3 months and associated with 2 or more of the following: Improvement with defecation Onset associated with change in frequency of stool Onset associated with change in consistency or form of stool Straining during defecation, dyspepsia, bloating and flatulence may be present	Abdominal tenderness Hard stool in the rectal vault	Clinical diagnosis ROME IV criteria Exclusion of organic causes based on laboratory investigations and imaging	Low FODMAP diet (fructose -when in excess of glucose, fructans, galacto-oligosaccharides, lactose and polyols (eg. sorbitol and mannitol), high dietary fiber, physical exercise Osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose for constipation predominant IBS Opioids such as loperamide and chloride channel activators such as linactolide and lubipristone for diarrhea predominant IBS Antispasmodicdrugs (e.g. anticholinergics such as hyoscyamine or dicyclomine), antidepressants and anxiolytics for pain predominant IBS

Differential diagnosis based on diarrhea

The following table outlines the major differential diagnoses based on diarrhea as the major presenting symptom:

Differential Diagnosis for Diarrhea predominant symptoms	Clinical features	Diagnosis
Crohn's disease	Diarrhea, abdominal pain	Colonoscopy, small bowel barium radiograph, CT enterography, magnetic resonance enterography
Ulcerative colitis	Present with abdominal pain, tenesmus, have diarrhea and rectal bleeding	Colonoscopy
Microscopic colitis	Watery diarrhea with nocturnal symptoms	Colonoscopy, flexible sigmoidoscopy and biopsy
Celiac disease	Diarrhea, steatorrhea, anemia	Endoscopy with small bowel biopsy, tissue transglutaminase antibody
Neuroendocrine tumor	Gastrinoma, carcinoid and VIP producing tumor	Urine 5HIAA, fasting gastrin levels (followed by secretin stimulation test), serum VIP
Hyperthyroidism	Increased appetite, insomnia, diarrhea, palpitations, heat intolerance, increased sweating	Serum TSH levels
Lactose intolerance	Flatulence, bloating with lactose consumption	Avoidance trial, lactose breath test
Infectious causes	Abdominal discomfort, diarrhea especially in the setting of recent travel	Stool for ova and parasites, stool Giardia antigen, stool culture, trial of metronidazole
Small bowel bacterial overgrowth	Bloating, diarrhea, abdominal distension	Jejunal aspirate, lactulose breath hydrogen test, antibiotic trial
Clostridium difficile infection(Psuedomembranous colitis)	Recent antibiotic treatment	Stool polymerase chain reaction

Differential diagnosis of irritable bowel syndrome on the basis of constipation:

The differential diagnosis of irritable bowel syndrome based on constipation as the predominant symptom is as follows:

Differential Diagnosis for Constipation predominant symptoms	Clinical features	Diagnosis
Strictures due to diverticultis,inflammatory bowel disease, ischemia or cancer	Obstipation, constipation	Barium enema, flexible sigmoidoscopy, colonoscopy, CT scan
Hypothyroidism	Fatigue, increased sensitivity to cold, dry skin, constipation, weight gain, puffy face, muscle weakness, hoarseness	Serum thyroid stimulating hormone levels
Medication	Opiates, cholestyramine, calcium-channel blockers, anticholinergic medications	Medication history.
Neurologic disease	Concurrent multiple sclerosis, Parkinson disease, autonomic dysfunction (Shy-Drager)	History and neurologic examination
Pelvic floor dysfunction	Straining, self digitation	Rectal examination, defecography, anorectal manometry, balloon expulsion study
Colonic inertia	Infrequent bowel movements	Radiopaque markers, scintigraphy, wireless pH and motility capsule

References

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