Differentiating celiac disease from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Differentiating Celiac Disease from Other Diseases

The table below summarizes the findings that differentiate causes of chronic diarrhea

Cause	Diarrhea		Age of onset	History			Physical exam	Lab findings	Additional finding	Cause	Gold standard dignosis
	Watery	Fatty		Weight loss	FTT	Abdominal pain
Celiac disease	+/-	+/-	Childhood Adult	+	+	+	Abdominal distention Tetany Mouth ulcers Dermatitis herpetiformis Signs of the fat-soluble vitamins A, D, E, and K deficiency	IgA endomysial antibody (IgA EMA) IgA tissue transglutaminase antibody (IgA tTG) IgG tissue transglutaminase antibody (IgG tTG) IgA deamidated gliadin peptide (IgA DGP) IgG deamidated gliadin peptide (IgG DGP)	Gluten-free diet	HLA-DQ2 and/or DQ8 gene mutation Innate responses to wheat proteins	Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody
Lactose intolerance	+	-	Adult	-	-	+	Abdominal tenderness	Stool osmotic gap of >125 mOsm/kg  Stool pH <6	Avoidance of dietary lactose Substitution to maintain nutrient intake Regulation of calcium intake Use of enzyme lactase	Acquired primary lactase deficiency Adult-type hypolactasia Lactase nonpersistence)	Lactose breath hydrogen test
Cystic fibrosis	-	+	Infancy and childhood	+	+	+	Digital clubbing Respiratory rale, wheeze, and crunckles Abdominal pain Cyanosis	Positive DNA analysis for CFTR multimutation method Evaluated nasal transepithelial potential difference (NPD)	Disease manifestations in multiple organ systems: Diabetes Recurrent upper and lower respiratory tract infections Infertility	Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein	Elevated sweat chloride ≥60 mmol/L
Laxative overuse	+	-	After childhood	+/-	-	+/-	enhanced gastrointestinal motility and gastrointestinal sound Mild abdominal tenderness Abdominal bloating	Hypokalemia  Metabolic alkalosis Hypermagnesemia(in case of magnesium laxative usage)	-	Laxative drug abuse	laxative screening on a stool for: Diphenolic laxatives (eg, bisacodyl) Polyethylene glycol-containing laxatives
Crohns disease	+	-	Young adults (20th)	+		+	Abdominal tenderness when palpated in severe disease Blood seen on rectal exam Fever Tachycardia Hypotension	Anemia Iron deficiency Elevated white blood cell count Vitamin B12 deficiency Elevated erythrocyte sedimentation rate Elevated CRP	Topical mucosamine and corticosteroids are preferred Mesalamine and sulfasalazine are used for remission	Abnormal immune response to self antigens	Colonoscopy with biopsy
Hyperthyroidism	+	-					Lump in the neck Proptosis Tremors Increased DTR				TSH with T3 and T4
VIPoma	+	-		+			Tachycardia Rash Facial flushing Abdominal distention Abdominal tenderness in the right upper abdominal quadrant		Dehydration Lethargy, muscle weakness Nausea, vomiting Flushing		Elevated VIP levels Followed by imaging
Irritable bowel syndrome	+	-					Abdominal tenderness Hard stool in the rectal vault		High dietary fiber Osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose Antispasmodic drugs (e.g. anticholinergics such as hyoscyamine or dicyclomine)		Clinical diagnosis ROME III criteria Pharmacologic studies based criteria
lactose intolerance	-	+					Abdominal tenderness when palpated in severe disease Fever Hypotension Tachycardia Nausea and vomiting	Bloating, Flatulence Symptoms begin mainly after ingestion of lactose			Lactose breath hydrogen test
Whipple disease	-	+		+	-	+		Leukocytopenia Thrombocytopenia	Skin hyperpigmentation Arthralgias		Upper endoscopy with biopsies of the small intestine for T. whipplei testing (histology with PAS staining, polymerase chain reaction [[[PCR]]] testing, and immunohistochemistry)
Allergic enteropathy/Food protein-induced enterocolitis syndrome (FPIES)	+	-	Infancy	+/-	+/-	+	Nausea Vomiting Abdominal distention	S/E: Blood-tinged and mucusy Polymorphonuclear leukocytes presence	triggered by cow's milk protein profuse, repetitive vomiting		oral food challenge (OFC)
Eosinophilic gastroenteritis	+	-	3rd decade	+/-	+/-	+	Nausea Vomiting Abdominal distention	elevated serum IgE levels abnormal D-xylose test	one-half of patients have other allergic diseases associated with an identifiable dietary antigen		eosinophilic infiltration of the gastrointestinal tract on biopsy
Microscopic colitis	+	-	6th decde	+	-	+	Abdominal tenderness	autoantibodies include: RF ANA AMA ANCA	Fecal urgency Incontinence My be associated with extraintestinal symptoms, such as: Arthralgia Arthritis Uveitis		A colonoscopy with mucosal biopsy with mononuclear infiltrates: Collagenous colitis is characterized by a colonic subepithelial collagen band >10 micrometers in diameter Lymphocytic colitis is characterized by ≥20 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells
Congenital chloride diarrhea	+	-	Neonate	+	+	-	-	Hyponatremia Hypochloremia Metabolic alkalosis	History of polyhydramnios Mutations in the SLC26A3 gene Encodes for an epithelial anion exchanger		Excessive fecal secretion of chloride
Congenital sodium diarrhea	+	-	Neonate	+	+	-	-	S/E: Alkaline Fecal sodium concentrations Serum: Metabolic acidosis Hyponatremia	May be associated with choanal or anal atresia
Glucose-galactose malabsorption	+	-	Infancy	+	+/-	+	Abdominal tenderness		severe life-threatening diarrhea Dehydration Symptomatic as long as the diet includes lactose or its hydrolysis products, glucose and galactose		positive glucose breath hydrogen test + normal intestinal biopsy
Abetalipoproteinemia	-	+	Infancy	+	+	+	Abdominal distention Impaired visual acuity and visual field defects Dysarthria	Low triglyceride Low total cholesterol levels  Acanthocytes  Low vitamin E levels	Clumsiness vision impairment Ataxia	autosomal recessive disorder caused by mutations encoding the microsomal triglyceride transfer protein (MTP)	Clinical findings and low triglyceride and cholesterol level
Primary bile acid malabsorption	+	+/-	Childhood Adolescents	+	+	+/-	-		Disease hetergenicity lead to varying presentation from chronic diarrhea without significant fat malabsorption to severe watery diarrhea and steatorrhea with malnutrition	genetic defects in SLC10A2 (solute carrier family 10 member 2 gene)	Total and specific bile acids from stool Gamma emitter selenium-75-homocholic acid taurine (SeHCAT)
Cause	Diarrhea		Age of onset	History			Physical exam	Lab findings	Additional finding	Cause	Gold standard dignosis
	Watery	Fatty		Weight loss	FTT	Abdominal pain
Gastrinoma (Zollinger-Ellison syndrome)	+	-	between the ages of 20 and 50	+	+/-	+	Mild to moderate upper abdominal tenderness	Positive secretin stimulation test Elevated serum chromogranin A	heartburn	Gastrin producing tumor mainly in duodenum	elevated basal or stimulated serum gastrin more than 1000 pg/mL

(solute-linked carrier famly 26 member A3)

oral food challenge (OFC):