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

Celiac disease must be differentiated from other diseases presenting as chronic diarrhea. The table below summarizes the findings that differentiate causes of chronic diarrhea

Cause	Diarrhea		Peak age of onset	History			Physical exam	Lab findings	Additional finding	Cause/Pathogenesis	Gold standard dignosis
	Watery	Fatty		Weight loss	FTT	Abdominal pain
Celiac disease	+/-	+/-	Childhood Adult	+	+	+	Abdominal distention Tetany Mouth ulcers Dermatitis herpetiformis	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 Signs of the fat-soluble vitamins A, D, E, and K deficiency	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 crackle 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 Tachycardia Hypotension	Anemia Iron deficiency Elevated white blood cell count Vitamin B12 deficiency Elevated erythrocyte sedimentation rate Elevated CRP	Blood seen on rectal exam Fever	Abnormal immune response to self antigens	Colonoscopy with biopsy
Hyperthyroidism	+	-	Any age	+	-	+/-	Lump in the neck Proptosis Tremors Increased DTR	Elevated T4 Elevated T3 Decreased level of TSH	Lid lag Sweating Hyperpigmentation	Graves' disease Hashimoto thyroiditis Toxic adenoma	TSH
VIPoma	+	-	Between 30 and 50	+	+/-	+/-	Tachycardia Rash Facial flushing Abdominal distention Abdominal tenderness in the right upper abdominal quadrant	Hypokalemia Hypochlorhydria or achlorhydria Low osmotic gap (<50 mOsm/kg)	Dehydration Lethargy, muscle weakness Nausea, vomiting Flushing	Primary secretory tumor	Elevated VIP levels Followed by imaging
Irritable bowel syndrome	+	-	Between 30 and 50	-	-	+	Abdominal tenderness Hard stool in the rectal vault	-	Bloating Flatulence	Postinfectious Inflammatory	Clinical diagnosis ROME III criteria Pharmacologic studies based criteria
Lactose intolerance	-	+	Any age	+	-	+/-	Abdominal tenderness when palpated in severe disease Fever Hypotension Tachycardia Nausea and vomiting	Lactose breath hydrogen test	Bloating Flatulence Symptoms begin mainly after ingestion of lactose	Reduction of lactase enzyme activity or lactase nonpersistence Congenital lactase deficiency	Lactase activity assay
Whipple disease	+/-	+	50th	+	-	+	Arthralgias of the large joints Hematochezia	Leukocytopenia Thrombocytopenia	Skin hyperpigmentation Arthralgias	Tropheryma whipplei	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	Stool examination: Blood-tinged and mucusy Polymorphonuclear leukocytes presence	Triggered by cow's milk protein Profuse, repetitive vomiting	Autoimmune/allergic response to food antigens	Oral food challenge (OFC)
Eosinophilic gastroenteritis	+	-	30th	+/-	+/-	+	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	Autoimmune/allergic response to food antigens	Eosinophilic infiltration of the gastrointestinal tract on biopsy
Microscopic colitis	+	-	60th	+	-	+	Abdominal tenderness	Elevatedautoantibodies include: RF ANA AMA ANCA	Fecal urgency Incontinence May be associated with extraintestinal symptoms, such as: Arthralgia Arthritis Uveitis	Mucosal immune responses to luminal factors in a genetically predisposed individual	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	+	+	-	-	Stool examination: Alkaline Fecal sodium concentrations Serum: Metabolic acidosis Hyponatremia	May be associated with choanal or anal atresia	Mutations in the SPINT2 gene	Clinical
Glucose-galactose malabsorption	+	-	Infancy	+	+/-	+	Abdominal tenderness	Stool examination: Acidic	Severe life-threatening diarrhea Dehydration Symptomatic as long as the diet includes lactose or its hydrolysis products, glucose and galactose	Mutations in solute carrier family 5, member 1 gene (SLC5A1, also known as SGLT1) Lead to deficiency in the intestinal sodium/glucose transporter	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	+	+	+/-	-	Low vitamins A, D, E, and K Anemia	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)
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