Whipple's disease differential diagnosis

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

Overview

Whipple's disease must be differentiated from other diseases that cause malabsorption, chronic diarrhea, multi system involvement, such as Celiac disease, systemic infections, and inflamatory bowel disease.

Differentiating Whipple's disease from other Diseases

Whipple's disease must be differentiated from other diseases that cause malabsorption, chronic diarrhea, joins involvement, and neurologic symptoms.

• Malabsorption with small intestine involvement (celiac disease, sarcoidosis, and lymphoma)
• Infections such as tuberculosis, endemic fungi (eg, Histoplasma spp), Rhodococcus and HIV infection
• Inflammatory bowel diseases
• Connective tissue diseases
• Addison's disease

The table below summarizes the diseases that cause malabsorption, diarrhea and abdominal pain.

Abbreviations: WBC: White blood cells; Plt: Platelets, Hgb: Hemoglobin, IgE: Immunoglobulin E, IgA: Immunoglobulin A

Cause	Peak age of onset	History					Physical exam	Lab findings				Additional findings	Cause/Pathogenesis	Gold standard diagnosis
		Fever	Abdominal pain	Diarrhea		Weight loss
				Watery	Fatty			WBC	Hgb	Plt	Other lab findings
Whipple's disease	40-60	±	+	+	+	+	Abnormal extraocular movement Lymphadenopathy Hyperpigmentation Decreased breathing sound	↓	↓	↓/↑	Hypoalbuminemia	Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Ascites Pleural effusion	Tropheryma whipplei HLA-B27	Small intestine biopsy for Tropheryma whipplei testing PCR testing
Celiac disease	Childhood Adult	-	+	+/-	+/-	+	Abdominal distention Tetany Mouth ulcers	-	↓	-	IgA endomysial antibody Anti-tissue transglutaminase antibody Anti-gliadin antibody	Signs of the fat-soluble vitamins A, D, E, and K deficiency Dementia Hepatosplenomegaly Ascites Dermatitis herpetiformis Must follow Gluten-free diet	HLA-DQ2 HLA-DQ8 Innate responses to wheat proteins	IgA endomysial antibody IgA tissue transglutaminase antibody
Cystic fibrosis	Childhood Adult	±	+	-	+	+	Digital clubbing Abnormal breathing sounds Cyanosis	-	↓	-	Positive DNA analysis for CFTR Evaluated nasal transepithelial potential difference (NPD)	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
Crohns disease	Young adults (20th)	+	+	+	+	+	Abdominal tenderness Tachycardia Hypotension	↑	↓	↑	Iron deficiency Vitamin B12 deficiency Elevated ESR Elevated CRP	Blood seen on rectal exam	Abnormal immune response to self antigens	Colonoscopy with biopsy
Irritable bowel syndrome	30-50	-	±	±	±	-	Abdominal tenderness Flatulence Hard stool in the rectal vault	-	-	-				Diagnosis of exclusion
VIPoma	30-50	-	+	+	+	+	Tachycardia Rash Facial flushing Abdominal distention Abdominal RUQ tenderness	-	-	-	Elevated VIP level Hypokalemia Hypochlorhydria or achlorhydria Low osmotic gap (<50 mOsm/kg)	Dehydration Lethargy Muscle weakness Nausea Vomiting	Primary secretory tumor	Elevated VIP levels Followed by imaging
Zollinger-Ellison syndrome	20-50	-	+	+	+	+	Abdominal tenderness	-	↓	-	Positive secretin stimulation test Elevated serum chromogranin A	Heartburn	Gastrin producing tumor mainly in duodenum	Elevated basal or stimulated serum gastrin> 120 pg/mL
Lactose intolerance	Any age	-	+	+	-	-	Abdominal tenderness Hypotension Tachycardia Nausea and vomiting	-	-	-	Hydrogen breath test	Bloating Flatulence Symptoms begin mainly after ingestion of lactose	Reduction of lactase enzyme activity or inability to produce persistent lactase Congenital lactase deficiency	Lactase activity assay
Eosinophilic gastroenteritis	30th	-	+	+	+	+	Abdominal distention	↑	-	-	Elevated serum IgE levels Eosinophilia Elevated ESR Hypoalbuminemia	Other allergic disorders Associated with an identifiable dietary antigen	Autoimmune allergic response to food antigens	Eosinophilic infiltration of the gastrointestinal tract on biopsy
Primary bile acid malabsorption	Childhood Adult	-	+	+	+	+		-	↓	-	Low vitamins A, D, E, and K		Genetic defects in SLC10A2 (solute carrier family 10 member 2 gene)	Elevated total and specific bile acids in stool Positive SeHCAT
Abetalipoproteinemia	Infancy Adult	-	+	+	+	+	Abdominal distension Visual field defect Dysarthria	-	-	-	Low triglyceride Low total cholesterol levels  Acanthocytes Low vitamin E levels	Visual impairment Ataxia	Autosomal recessive disorder caused by mutations encoding the microsomal triglyceride transfer protein (MTP)	Clinical findings and low triglyceride and cholesterol level
Microscopic colitis	50-70	-	+	+	-	+	Abdominal tenderness	-	↓	-	Elevated autoantibodies include: RF ANA AMA ANCA	Fecal urgency Fecal incontinence Arthralgia Arthritis Uveitis	Mucosal immune responses to luminal factors in a genetically predisposed individual	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
Hyperthyroidism	Any age	±	+	+	-	+	Lump in the neck Proptosis Tremor Increased DTR	-	-	-	Elevated T4 Elevated T3 Decreased TSH	Lid lag Sweating Hyperpigmentation	Graves' disease Hashimoto's thyroiditis Toxic adenoma	TSH
Grain allergy	Childhood	-	+	+	-	+	Vomiting Abdominal distension	-	-	-	Elevated IgE	Atopic dermatitis Dysphagia	Abnormal immune response to wheat antigens	Measurement of grain-specific immunoglobulin E (IgE)