Chronic diarrhea differential diagnosis

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Case #1

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

Overview

The differential diagnosis for chronic diarrhea is enormous, with a large number of diagnostic tests available that can be used to evaluate these patients. Classifying the patient with chronic diarrhea into a subcategory helps to direct the diagnostic work-up.

Differential diagnosis

It is important to differentiate chronic diarrhea based on the kind of diarrhea that is produced. Chronic diarrhea can be subdivided into three major types; watery, fatty, inflammatory. Watery chronic diarrhea can then further be sub-divided into osmotic or secretory diarrhea. Below is a list of differential diagnosis of chronic diarrhea by stool characteristics.

Watery

• Secretory (often nocturnal; unrelated to food intake; fecal osmotic gap < 50 mOsm per kg*)
  • Alcoholism
  • Bacterial enterotoxins (e.g., cholera)
  • Bile acid malabsorption
  • Brainerd diarrhea (epidemic secretory diarrhea)
  • Congenital syndromes
  • Crohn disease (early ileocolitis)
  • Endocrine disorders e.g., hyperthyroidism
  • Medications (see causes section)
  • Microscopic colitis (lymphocytic and collagenous subtypes)
  • Neuroendocrine tumors (e.g., gastrinoma, vipoma, carcinoid tumors, mastocytosis)
  • Nonosmotic laxatives (e.g., senna, docusate sodium)
  • Postsurgical (e.g., cholecystectomy, gastrectomy, vagotomy, intestinal resection)
  • Vasculitis
• Osmotic (fecal osmotic gap > 125 mOsm per kg*)
  • Carbohydrate malabsorption syndromes (e.g., lactose, fructose)
  • Celiac disease
  • Osmotic laxatives and antacids (e.g., magnesium, phosphate, sulfate)
  • Sugar alcohols (e.g., mannitol, sorbitol, xylitol)
• Functional (distinguished from secretory types by hypermotility, smaller volumes, and improvement at night and with fasting)
  • Irritable bowel syndrome

Cause			Osmotic gap		History	Physical exam	Gold standard	Treatment
			< 50 mOsm per kg	> 125 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 prefferd Mesalamine and sulfasalazine are used for remission
		Hyperthyroidism	+	-	Excessive sweating Heat intolerance Increased bowel movements	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	Tachycardia Rash Facial flushing Abdominal distention Abdominal tenderness in the right upper abdominal quadrant	Elevated VIP levels 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 enzyme lactase
		Celiac disease	-	+	May be asymptomatic Vague abdominal pain Diarrhea Weight loss Malabsorption / steatorrhea Bloatedness	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 Ab	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: Improves with defecation Onset associated with change in frequency of stool Onset associated with change in appearance of stool 25% of bowel movements are loose stools History of straining is also common	Abdominal tenderness Hard stool in the rectal vault	Clinical diagnosis ROME III criteria Pharmacologic studies based criteria	High dietary fiber Osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose antispasmodic drugs (e.g. anticholinergics such as hyoscyamine or dicyclomine)

Fatty (bloating and steatorrhea in many, but not all cases)

• Malabsorption syndrome (damage to or loss of absorptive ability)
  • Amyloidosis
  • Carbohydrate malabsorption (e.g., lactose intolerance)
  • Celiac sprue (gluten enteropathy)–various clinical presentations
  • Gastric bypass
  • Lymphatic damage (e.g., congestive heart failure, some lymphomas)
  • Medications (e.g., orlistat Xenical; inhibits fat absorption, acarbose Precose; inhibits carbohydrate absorption])
  • Mesenteric ischemia
  • Noninvasive small bowel parasite (e.g., Giardia)
  • Postresection diarrhea
  • Short bowel syndrome
  • Small bowel bacterial overgrowth (> 105 bacteria per mL)
  • Tropical sprue
  • Whipple disease (Tropheryma whippelii infection)
• Maldigestion (loss of digestive function)
  • Hepatobiliary disorders
  • Inadequate luminal bile acid
  • Loss of regulated gastric emptying
  • Pancreatic exocrine insufficiency

Inflammatory or exudative (elevated white blood cell count, occult or frank blood or pus)

• Inflammatory bowel disease Crohn disease (ileal or early Crohn disease may be secretory)
  • Diverticulitis
  • Ulcerative colitis
  • Ulcerative jejunoileitis
• Invasive infectious diseases
  • Clostridium difficile (pseudomembranous) colitis–antibiotic history
  • Invasive bacterial infections (e.g., tuberculosis, yersiniosis)
  • Invasive parasitic infections (e.g., Entamoeba)–travel history
  • Ulcerating viral infections (e.g., cytomegalovirus, herpes simplex virus)
• Neoplasia
  • Colon carcinoma
  • Lymphoma
  • Villous adenocarcinoma
• Radiation colitis

References

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