Chronic diarrhea, fever, and abdominal pain differential diagnosis

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

Differential Diagnosis of Chronic Diarrhea, Fever, and Abdominal Pain from other Diseases

The following table outlines the major differential diagnoses of chronic diarrhea, fever, and abdominal pain.

Abbreviations: GI: Gastrointestinal, CBC: Complete blood count, WBC: White blood cell, RBC: Red blood cell, Plt: Platelet, Hgb: Hemoglobin, ESR: Erythrocyte sedimentation rate, CRP: C–reactive protein, IgE: Immunoglobulin E, IgA: Immunoglobulin A, ETEC: Escherichia coli enteritis, EPEC: Enteropathogenic Escherichia coli, EIEC: Enteroinvasive Escherichia coli, EHEC: Enterohemorrhagic Escherichia coli, EAEC: Enteroaggregative Escherichia coli, Nl: Normal, ASCA: Anti saccharomyces cerevisiae antibodies, ANCA: Anti–neutrophil cytoplasmic antibody, DNA: Deoxyribonucleic acid, CFTR: Cystic fibrosis transmembrane conductance regulator, SLC10A2: Solute carrier family 10 member 2, SeHCAT: Selenium homocholic acid taurine or tauroselcholic acid, IEL: Intraepithelial lymphocytes, MRCP: Magnetic resonance cholangiopancreatography, ANA: Antinuclear antibodies, AMA: Anti-mitochondrial antibody, LDH: Lactate dehydrogenase, CPK: Creatine phosphokinase, PCR: Polymerase chain reaction, ELISA: Enzyme–linked immunosorbent assay, LT: Heat–labile enterotoxin, ST: Heat–stable enterotoxin, RT-PCR: Reverse–transcriptase polymerase chain reaction, CD4: Cluster of differentiation 4, HIV: Human immunodeficiency virus, RUQ: Right-upper quadrant, VIP: Vasoactive intestinal peptide, GI: Gastrointestinal, FAP: Familial adenomatous polyposis, HNPCC: Hereditary nonpolyposis colorectal cancer, MTP: Microsomal triglyceride transfer protein, Scl‑70: Anti–topoisomerase I, TSH: Thyroid-stimulating hormone, T4: Thyroxine, T3: Triiodothyronine, DTR: Deep tendon reflex, RNA: Ribonucleic acid

Cause		Clinical manifestation									Lab findings									Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
		Symptoms								GI signs
		Duration		Diarrhea			Fever	Abdominal pain	Weight loss
											Stool exam					CBC			Other lab findings
		Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
Crohn's disease		–	+	+	+	+	±	+	+	Abdominal tenderness Oral mucosal lesions	+	+	–	Nl	–	↑	↓	↑	Anti saccharomyces cerevisiae antibodies (ASCA) Vitamin B12 deficiency Elevated ESR Elevated CRP	Uveitis Arthritis Erythema nodosum Pyoderma gangrenosum Amyloidosis Venous and arterial thromboembolism Renal stones Bronchiectasis	Abnormal immune response to self antigens	Colonoscopy with biopsy
Ulcerative colitis		–	+	+	+	+	±	+	+	Abdominal tenderness Blood on rectal examination	+	+	–	Nl	–	↑	↓	↑	Anti–neutrophil cytoplasmic antibody (P–ANCA) Hypoalbuminemia Hypokalemia Hypomagnesemia Elevated ESR Elevated CRP	Skin rash Iritis Uveitis Seronegative arthritis Clubbing Erythema nodosum	Abnormal immune response to self antigens	Colonoscopy with biopsy
Cystic fibrosis		–	+	–	–	+	±	+	+	Abdominal distention Hepatosplenomegaly Rectal prolapse	–	–	–	Nl	Fat droplets on sudan stain	Nl	↓	Nl	Positive DNA analysis for cystic fibrosis transmembrane conductance regulator (CFTR) Nasal transepithelial potential difference Fat soluble vitamins deficiency	Malabsorption Recurrent respiratory tract infection Bronchiectasis Diabetes mellitus Scoliosis Infertility	Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein	Positive genetic testing Elevated sweat chloride ≥60 mmol/L
Cause		Duration		Diarrhea			Fever	Abdominal pain	Weight loss	GI signs	Stool exam					CBC			Other lab findings	Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
		Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
Infective colitis		–	+	+	+	–	+	+	+	Rebound abdominal tenderness	+	+	+	Nl	Positive stool culture Positive fecal calprotectin Positive fecal lactoferrin	↑	↓	↑	Elevated CRP Elevated ESR	Arthritis Uveitis	Salmonella Shigella Campylobacter E. coli 0157:H7 Clostridium difficile Entamoeba histolytica Adenovirus Cytomegalovirus Herpes simplex virus	Stool culture Blood culture
Ischemic colitis		+	+	+	+	–	+	+	+	Hyperactive then absent bowel sounds Abdominal tenderness	+	+	–	Nl	–	↑	↓	↑	Elevated CRP Elevated ESR Elevated serum lactate Elevated lactate dehydrogenase (LDH)  Elevated creatine phosphokinase (CPK) Elevated amylase Hypoalbuminemia	IgA vasculitis	Hypercoagulability  Nonocclusive colonic ischemia Embolic and thrombotic arterial occlusion Mesenteric vein thrombosis	Abdominal CT scan
Cause		Duration		Diarrhea			Fever	Abdominal pain	Weight loss	GI signs	Stool exam					CBC			Other lab findings	Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
		Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
Whipple's disease		–	+	+	–	+	±	+	+	Hepatosplenomegaly Ascites	–	–	–	Nl	Positive fecal fat	↓	↓	↓/↑	Hypoalbuminemia Fat soluble vitamins deficiency	Malabsorption Abnormal extraocular movement Lymphadenopathy Hyperpigmentation Uveitis Endocarditis Encephalitis Dementia Pleural effusion	Tropheryma whipplei	Small intestine biopsy for Tropheryma whipplei testing PCR testing
Tropical sprue		+	+	+	–	+	+	+	+	Angular stomatitis Oral mucosal lesion	+	–	–	Nl	Positive stool culture	Nl	↓	Nl	Fat soluble vitamins deficiency Vitamin B12 deficiency Folate deficiency Hypokalemia	Myalgia Neuropathy Edema	Escherichia coli Klebsiella pneumoniae Enterobacter cloacae	Diagnosis of exclusion
Salmonellosis		+	+	+	+	–	+	+	–	Abdominal distention Diffuse abdominal tenderness Hepatosplenomegaly	+	+	–	Nl	Positive stool culture Positive serologic testing	↑	Nl	↑	Hypokalemia Hypernatremia Hyponatremia Hypercalciuria Hypocitraturia	Post–infectious arthritis Obtundation Bacteremia Pericarditis Pyelonephritis Brain abscess	Salmonella	Stool culture
Cause		Duration		Diarrhea			Fever	Abdominal pain	Weight loss	GI signs	Stool exam					CBC			Other lab findings	Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
		Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
Escherichia coli enteritis	EPEC	+	+	+	+	–	+	+	+	Diffuse abdominal tenderness	+	+	–	Nl	Positive stool culture	↑	Nl	Nl	–	–	Enteropathogenic E. coli	DNA probe or polymerase chain reaction (PCR) of the EPEC adherence factor Stool culture
Aeromonas		+	+	+	+	–	+	+	–	Abdominal distention Hyperactive bowel sounds Diffuse abdominal tenderness	+	+	–	Nl	Positive stool culture	↑	Nl	Nl	–	Wound infection Bacteremia Hemolytic uremic syndrome  Meningitis Ocular infection Pneumonia  Urinary tract infection Osteomyelitis Peritonitis Acute cholecystitis Opportunistic infections in immunocompromised patients	Aeromonas virulence factors including endotoxins, hemolysins, enterotoxins, and adherence factors	Blood culture Wound culture
Mycobacterium avium complex		+	+	+	+	–	+	+	–	Abdominal distention Hepatosplenomegaly	+	+	–	Nl	–	↓	↓	Nl	Elevated liver enzymes	Opportunistic infection in immunocompromised patients Pulmonary infection Adenopathy  Night sweats	Mycobacterium avium complex	Blood culture
Cause		Duration		Diarrhea			Fever	Abdominal pain	Weight loss	GI signs	Stool exam					CBC			Other lab findings	Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
		Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
CMV colitis		+	+	–	+	–	±	+	–	Diffuse abdominal tenderness	+	+	–	Nl	Viral antigen assay	↓	Nl	Nl	Decreased CD4 level Abnormal liver function test	Encephalitis  Guillain–Barré syndrome Pneumonia  Retinitis Pericarditis and myocarditis Atherosclerosis  Venous thrombosis	Cytomegalovirus	Quantitative PCR tests
HIV		–	+	+	–	–	+	+	+	Abdominal distention Diffuse abdominal tenderness	+	–	–	Nl	–	↓	↓	Nl	Decreased CD4 level Electrolyte imbalance	Lymphadenopathy Disseminated infection	HIV	HIV virologic (viral load) test Immunoassay
Entamoeba histolytica		+	+	+	+	–	+	+	–	Abdominal distention Diffuse abdominal tenderness	+	+	+	Nl	–	↑	Nl	Nl	–	Liver abscess Pleuropulmonary infection Cardiac infection Brain abscess Cutaneous infection	Entamoeba histolytica	Antigen testing Serology
Microsporidia		+	+	+	–	–	+	+	–	Abdominal distention Diffuse abdominal tenderness	–	–	+	Nl	Positive stool microscopy	Nl	Nl	Nl	Decreased CD4 count	Malabsorption Keratitis  Seizure Myositis	Microsporidia	Antigen detection assays
Cause		Duration		Diarrhea			Fever	Abdominal pain	Weight loss	GI signs	Stool exam					CBC			Other lab findings	Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
		Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
Isospora		+	+	+	–	+	+	+	+	Abdominal distention Diffuse abdominal tenderness	+	+	+	Nl	Positive stool microscopy Positive fecal fat	↑	Nl	Nl	Elevated eosinophils  Hypokalemia Increased creatinine	Chronic illness in immunocompromised patients	Isospora	Detecting oocysts in the feces
Lymphoma		–	+	+	+	–	+	+	+	Diffuse abdominal tenderness Hepatosplenomegaly	–	+	–	Nl	–	Nl	↓	Nl	Paraproteinemia	Malabsorption Lactose intolerance Ascites	Primary tumor of GI tract	Colonoscopy with biopsy
Medications ACE inhibitors Digoxin Cephalosporins Statins Thiazide diuretics Triptans Lactulose Anti retroviral agents Chemotherapeutic agents Antifungals Magnesium		+	+	+	–	±	±	+	+	Abdominal distention Dehydration	–	–	–	↑/↓	–	↑	Nl	Nl	Elevated plasma level of drug	–	Inflammation Pseudomembranous colitis	Clinical evaluation after discontinuation of the drugs