Diarrhea

| Resident
Survival
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Diarrhea Microchapters

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Overview

Patient Information

Classification

Acute Diarrhea
Chronic diarrhea

Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief:  Usama Talib, BSc, MD [2], Sadaf Sharfaei M.D.[3], Seyedmahdi Pahlavani, M.D. [4], Cafer Zorkun, M.D., Ph.D. [5], M.Umer Tariq [6]

Synonyms and keywords: Loose stools

## Overview

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Diarrhea is defined as the passage of unformed or abnormally liquid stools at an increased frequency. Diarrhea can be classified as acute or chronic. Acute diarrhea has a duration of less than 2 weeks and may be classified on the basis of etiology and presentation. On the basis of etiology, acute diarrhea may be classified into infectious and non-infectious subtypes. Subacute diarrhea is defined as a diarrhea lasting for two to four weeks. Although chronic diarrhea has multiple definitions, a current working definition is the production of loose stools for longer than 4 weeks. Frequent defecation with normal consistency is termed psuedo-diarrhea. There are 3 basic categories of chronic diarrhea: watery, fatty (malabsorption), and inflammatory (with blood and pus). The diagnosis is based on duration of symptoms, signs, microscopic stool examination and culture, stool osmolarity, and in some rare instances colonoscopy. The treatment is mainly based on severity of symptoms, etiology and availability of medications. Prevention is based on proper maintaining the filtration systems at water plants, hand wash, and effectively use of alcohol-based hand sanitizers. Vaccination for some viruses, such as Rotavirus is a part of preventive measures.

## Classification

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Diarrhea can be classified as acute or chronic depending on the duration of onset of symptoms. Acute and chronic diarrhea can be further classified as follows:

### Classification of Acute Diarrhea

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| Acute diarrhea|

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| Infectious|

| Non-Infectious|

| Bacterial|

| Viral|

| Fungal|

| Protozoa|

| Medications|

| Poisoning|

| Systemic illness|

### Classification of Chronic Diarrhea

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| Chronic diarrhea|

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| Watery|

| Inflammatory|

| Secretory|

| Osmotic|

## Differential Diagnosis of Diarrhea of other diseases

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To review the differential diagnosis of diarrhea, click here.

To review the differential diagnosis of acute diarrhea, click here.

To review the differential diagnosis of chronic diarrhea, click here.

To review the differential diagnosis of traveler's diarrhea, click here.

To review the differential diagnosis of acute watery diarrhea, click here.

To review the differential diagnosis of acute bloody diarrhea, click here.

To review the differential diagnosis of acute fatty diarrhea, click here.

To review the differential diagnosis of chronic watery diarrhea, click here.

To review the differential diagnosis of chronic bloody diarrhea, click here.

To review the differential diagnosis of chronic fatty diarrhea, click here.

To review the differential diagnosis of acute diarrhea and fever, click here.

To review the differential diagnosis of chronic diarrhea and fever, click here.

To review the differential diagnosis of acute diarrhea and abdominal pain, click here.

To review the differential diagnosis of chronic diarrhea and abdominal pain, click here.

To review the differential diagnosis of acute diarrhea and weight loss, click here.

To review the differential diagnosis of chronic diarrhea and weight loss, click here.

To review the differential diagnosis of acute diarrhea, fever, and abdominal pain, click here.

To review the differential diagnosis of chronic diarrhea, fever, and abdominal pain, click here.

To review the differential diagnosis of acute diarrhea, abdominal pain, and weight loss, click here.

To review the differential diagnosis of chronic diarrhea, abdominal pain, and weight loss, click here.

### Diarrhea

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The following table outlines the major differential diagnoses of diarrhea.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

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

Categories  | Cause  | Clinical manifestation | Lab findings | Extra intestinal findings  | Cause/Pathogenesis  | Gold standard diagnosis

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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
Gastrointestinal  | 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

Celiac disease | –  | \+  | ±  | –  | ±  | –  | \+  | \+  |

* Abdominal distention
* Increased bowel sounds
* Oral mucosal lesions
* Hepatosplenomegaly
* Ascites

| –  | –  | –  | Nl  |

* Fat droplets on sudan stain

| Nl  | ↓  | Nl  |

* IgA endomysial antibody
* Anti–tissue transglutaminase antibody
* Anti–gliadin antibody
* Fat soluble vitamins deficiency

* Malabsorption
* Dementia
* Dermatitis herpetiformis

* HLA–DQ2
* HLA–DQ8
* Innate responses to wheat proteins

* IgA endomysial antibody
* Anti–tissue transglutaminase antibody

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
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

Chronic pancreatitis | –  | \+  | \+  | –  | \+  | –  | \+  | \+  |

* Abdominal tenderness

| –  | –  | –  | Nl  |

* Fat droplets on sudan stain
* Positive fecal elastase measurement

| Nl  | Nl  | Nl  |

* Slightly elevated amylase and lipase
* Abnormal pancreatic function test
* Secretin stimulation test

* Malabsorption
* Diabetes mellitus
* Pancreatic pseudocyst

* Toxins
* Recurrent acute pancreatitis
* Genetic predesposition
* Autoimmune

* Magnetic resonance cholangiopancreatography (MRCP)

Bile acid malabsorption | –  | \+  | \+  | –  | \+  | –  | –  | \+  |  | –  | –  | –  | Nl  |

* Fat droplets on sudan stain

| Nl  | Nl  | Nl  |

* Reduced cholesterol level

* Malabsorption
* Hypotension
* Tachycardia

* Genetic defects in SLC10A2

* SeHCAT test

Microscopic colitis | –  | \+  | \+  | –  | –  | –  | \+  | \+  |

* Abdominal tenderness
* Fecal incontinence

| –  | –  | –  | Nl  | –  | Nl  | ↓  | Nl  |

* Hypokalemia
* Elevated CRP
* Positive autoantibodies include:
* RF
* ANA
* AMA
* ANCA

* Arthritis
* Uveitis
* Idiopathic thrombocytopenic purpura
* Pleuro pericarditis
* Hypothyroidism
* Psoriasis

* Mucosal immune responses to luminal factors in a genetically predisposed individual
* Drug–induced

* 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

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

Lactose intolerance | \+  | \+  | \+  | –  | –  | –  | \+  | –  |

* Abdominal tenderness
* Abdominal distention

| –  | –  | –  | ↑  | –  | Nl  | Nl  | Nl  |

* Lactose tolerance test
* Genetic testing

* Headache
* Vertigo
* Memory impairment
* Lethargy

* Reduction of lactase enzyme activity or inability to produce persistent lactase
* Congenital lactase deficiency
* Secondary lactose malabsorption

* Small bowel biopsy
* Lactose breath hydrogen test

Irritable bowel syndrome | –  | \+  | ±  | –  | ±  | –  | ±  | –  |

* Abdominal tenderness
* Abdominal distention
* Normal bowel sounds

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  | Nl  |

* Anxiety
* Palpitation

* Unknown

* Diagnosis of exclusion

Infection  | Bacterial  | 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

Small bowel bacterial overgrowth | –  | \+  | \+  | –  | \+  | –  | \+  | \+  |

* Abdominal distention

| \+  | –  | –  | Nl  |

* Positive stool culture
* Positive fecal fat

| Nl  | ↓  | Nl  |

* Hypoalbuminemia
* Abnormal hydrogen breath test
* Lactic acidosis

* Malabsorption
* Rosacea

* Excess bacteria in the small intestine
* Alterations in intestinal anatomy or GI motility

* Diagnosis of exclusion

Pseudomembranous enterocolitis | \+  | –  | \+  | ±  | –  | \+  | \+  | ±  |

* Generalized abdominal tenderness
* Abdominal distention
* Rebound abdominal tenderness

| \+  | \+  | –  | Nl  |

* Enzyme–linked immunosorbent assay (ELISA)
* Polymerase chain reaction (PCR) assay or C. difficile antigen

| ↑  | ↓  | ↓  |

* Elevated serum creatinine
* Hypoalbuminemia
* Elevated lactic acid

* Dehydration
* Acute kidney injury

* Bacteremia
* Reactive arthritis
* Necrotizing fasciitis

* Clostridium difficile
* Recent antibiotics use
* Recent surgery

* Stool exam
* Pseudomembranes on colonoscopy

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
Campylobacteriosis | \+  | –  | \+  | \+  | –  | \+  | \+  | –  |

* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  | Nl  |

* Toxic megacolon
* Sepsis
* Arthritis
* Endocarditis
* Guillain–Barré syndrome

* Campylobacter jejuni

* Stool culture

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

Shigellosis | \+  | –  | \+  | \+  | –  | \+  | \+  | –  |

* Abdominal distention
* Hyperactive bowel sounds
* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑/↓  | ↓  | ↓  |

* Elevated CRP
* Elevated ESR
* Hyponatremia
* Hypoglycemia
* Azotemia

* Headache
* Lethargy
* Seizures
* Delirium
* Post–infectious arthritis
* Myocarditis

* Shigella

* 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 | ETEC

(Traveler's diarrhea)

| \+  | –  | \+  | –  | –  | \+  | –  | –  |

* Diffuse abdominal tenderness

| \+  | –  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  | –  | –  |

* Enterotoxigenic escherichia coli
* Enterotoxins:
* Heat–labile enterotoxin (LT)
* Heat–stable enterotoxin (ST)

* Stool culture

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

EIEC | \+  | –  | \+  | \+  | –  | \+  | \+  | –  |

* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  | –  | –  |

* Enteroinvasive E. coli

* DNA probe
* Stool culture

EHEC | \+  | –  | \+  | \+  | –  | –  | \+  | –  |

* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑  | ↓  | ↓  |

* Azotemia

* Hemolytic uremic syndrome (HUS)
* Renal failure

* Enterohemorrhagic E. coli
* Shiga toxins

* Stool culture

EAEC | \+  | \+  | \+  | \+  | –  | –  | \+  | –  |

* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑  | ↓  | ↓  | –  |

* Chronic infection in immunocompromised patients

* Enteroaggregative E. coli

* 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
Yersinia enterocolitica | \+  | –  | \+  | \+  | –  | \+  | \+  | –  |

* Abdominal distention
* Hyperactive bowel sounds
* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  | –  |

* Bacteremia
* Reactive arthritis
* Glomerulonephritis
* Endocarditis
* Erythema nodosum
* Abscess

* Yersinia enterocolitica

* Stool culture

Vibrio cholera | \+  | –  | \+  | –  | –  | –  | \+  | –  |  | \+  | –  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  |

* Azotemia

* Severe dehydration
* Decreased skin turgor
* Oliguria
* Renal failure
* Muscle cramps
* Seizure
* Somnolence

* Cholera toxin

* 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

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
Plesiomonas | \+  | –  | \+  | \+  | –  | \+  | \+  | –  |

* Hyperactive bowel sounds
* Diffuse abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  | –  |

* Opportunistic infections in immunocompromised patients or hepatobiliary disease
* Bacteremia
* Cellulitis and skin abscesses
* Peritonitis
* Meningoencephalitis
* Ocular infection
* Pneumonia
* Prosthetic joint infection
* Septic abortion

* Plesiomonas shigelloides

* Blood 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

Food poisoning

* Staphylococcus aureus
* Bacillus cereus
* Clostridium perfringens

| \+  | –  | \+  | ±  | –  | \+  | \+  | ±  |

* Abdominal distention

| \+  | ±  | –  | Nl  |

* Positive stool culture

| ↑  | Nl  | Nl  | –  |

* History of travel or ingestion of infected food

* Enterotoxins

* Stool culture

Virus  | 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
Norovirus | \+  | –  | \+  | –  | –  | \+  | \+  | –  |

* Abdominal distention

| –  | –  | –  | Nl  |

* Positive stool reverse–transcriptase polymerase chain reaction (RT–PCR)

| ↓  | Nl  | Nl  | –  |

* Myalgia
* Headache
* Seizure
* Encephalopathy

* Norovirus

* Clinical diagnosis

Rotavirus | \+  | –  | \+  | –  | –  | \+  | –  | –  |

* Hyperactive bowel sounds
* Diffuse abdominal tenderness

| \+  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  |

* Elevated blood urea nitrogen
* Hyperchloremic acidosis
* Hypocalcemia

* Necrotizing enterocolitis
* Intussusception
* Biliary atresia
* Central nervous system involvement

* Rotavirus

* Stool immune–based assays

Echovirus | \+  | –  | \+  | –  | –  | \+  | \+  | –  |

* Abdominal distention

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  | –  |

* Liver failure
* Myocarditis

* Echovirus

* Clinical diagnosis

Adenovirus | \+  | –  | \+  | –  | –  | \+  | \+  | –  |

* Abdominal distention

| –  | –  | –  | Nl  |

* Viral antigen assay

| Nl  | Nl  | Nl  | –  |

* Respiratory disease
* Follicular conjunctivitis
* Epidemic keratoconjunctivitis
* Hepatitis
* Urethritis
* Myocarditis
* Meningitis
* Bacteremia

* Adenovirus

* Clinical diagnosis

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

Parasite  | 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
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

Giardia | –  | \+  | \+  | –  | \+  | –  | \+  | \+  |

* Abdominal distention
* Diffuse abdominal tenderness

| –  | –  | \+  | Nl  | –  | Nl  | Nl  | Nl  | –  |

* Malabsorption
* Urticaria
* Depression

* Giardia lamblia

* Antigen detection assays

Cryptosporidium | –  | \+  | \+  | –  | –  | –  | \+  | \+  |

* Abdominal distention
* Diffuse abdominal tenderness

| –  | –  | \+  | Nl  |

* Positive stool microscopy

| Nl  | Nl  | Nl  |

* Elevated alkaline phosphatase

* Chronic, life–threatening illness in immunocompromised patients

* Cryptosporidium

* Polymerase chain reaction

Microsporidia | \+  | \+  | \+  | –  | –  | \+  | \+  | –  |

* Abdominal distention
* Diffuse abdominal tenderness

| –  | –  | \+  | Nl  |

* Positive stool microscopy

| Nl  | Nl  | Nl  |

* Decreased CD4 count

* Malabsorption
* Keratitis
* Seizure
* Myositis

* Microsporidia

* Antigen detection assays

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

Tumors  | 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
Carcinoid tumor | –  | \+  | \+  | \+  | –  | –  | \+  | \+  |

* Abdominal distention

| –  | \+  | –  | ↓  | –  | Nl  | Nl  | Nl  |

* Elevated urinary 5–hydroxyindoleacetic acid (5–HIAA) level
* High chromogranin A

* Facial flushing
* Jaundice
* Edema
* Valvular heart disease
* Right–sided heart failure

* Well–differentiated neuroendocrine tumor

* Blood chromogranin A level

VIPoma | \+  | \+  | \+  | –  | \+  | –  | \+  | \+  |

* Abdominal distention
* Abdominal RUQ tenderness
* Nausea
* Vomiting

| –  | –  | –  | ↓  | –  | Nl  | Nl  | Nl  |

* Elevated VIP level
* Hypokalemia
* Hypochlorhydria or achlorhydria
* Low osmotic gap (<50 mOsm/kg)

* Rash
* Facial flushing
* Dehydration
* Lethargy
* Muscle weakness

* Primary secretory tumor

* Blood VIP levels
* Followed by imaging

Zollinger–Ellison syndrome | –  | \+  | \+  | \+  | \+  | –  | \+  | \+  |

*     * Epigastric tenderness

| –  | –  | –  | ↓  | –  | Nl  | ↓  | Nl  |

* Positive secretin stimulation test
* Elevated serum chromogranin A

*     * Jaundice

* Gastrin producing tumor mainly in duodenum

* Secretin stimulation test

Somatostatinoma | –  | \+  | \+  | –  | –  | –  | \+  | \+  |

*     * Epigastric tenderness

| –  | –  | –  | ↓  | –  | Nl  | Nl  | Nl  |

* Elevated fasting plasma somatostatin

*     * Diabetes mellitus
* Cholelithiasis
* Jaundice

* Neuroendocrine tumors of D–cell origin

* Plasma somatostatin level
* Followed by imaging

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
Lymphoma | –  | \+  | \+  | \+  | –  | \+  | \+  | \+  |

* Diffuse abdominal tenderness
* Hepatosplenomegaly

| –  | \+  | –  | Nl  | –  | Nl  | ↓  | Nl  |

* Paraproteinemia

* Malabsorption
* Lactose intolerance
* Ascites

* Primary tumor of GI tract

* Colonoscopy with biopsy

Colorectal cancer | –  | \+  | \+  | \+  | \+  | –  | \+  | \+  |

* Diffuse abdominal tenderness

| –  | \+  | –  | Nl  | –  | Nl  | ↓  | Nl  |

* Positive carcinoembryonic antigen

* Metastasis

* FAP gene
* HNPCC gene

*     * Colonoscopy and biopsy

Medication/Toxicity  | 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

Factitious diarrhea  | \+  | \+  | \+  | –  | –  | –  | \+  | \+  |

* Abdominal distention

| –  | –  | –  | ↑/↓  | –  | Nl  | Nl  | Nl  |

* Hypokalemia
* Metabolic alkalosis
* Hypermagnesemia

* Malabsorption
* Lethargy
* Generalized weakness
* Acute renal failure

* Medications

* Clinical evaluation after discontinuation of the drugs

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
Heavy metal ingestion | –  | \+  | \+  | –  | –  | –  | \+  | \+  |

* Abdominal distention

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  |

* Elevated plasma heavy metal level

* Headache
* Numbness
* Alopecia
* Vertigo

* Heavy metal ingestion

* Plasma level of heavy metal

Organophosphate poisoning | \+  | \+  | \+  | –  | –  | –  | \+  | –  |

* Salivation
* Vomiting

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  |

* Reduced RBC acetylcholinesterase
* Plasma cholinesterase activity

* Autonomic dysfunction
* Motor deficit
* Sensory deficit
* Bronchospasm
* Urination
* Miosis
* Bradycardia
* Lacrimation
* Sweating
* Cardiac arrhythmias
* Acute renal injury

* Neurotoxins bind to acetylcholinesterase (AChE)

* Clinical diagnosis

Opium withdrawal | \+  | \+  | \+  | –  | –  | –  | \+  | –  |

* Hyperactive bowel sounds

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  |

* Azotemia
* Hypokalemia
* Metabolic alkalosis

* Dysphoria
* Restlessness
* Sweating
* Rhinorrhea
* Lacrimation
* Myalgia
* Arthralgia

* Opium withdrawal

* Clinical diagnosis following opium withdrawal

Iatrogenic  | 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
Short bowel syndrome | \+  | \+  | \+  | –  | \+  | –  | –  | \+  |

* Abdominal distention
* Abdominal tenderness

| –  | –  | –  | Nl  |

* Positive fecal fat

| Nl  | ↓  | ↑  |

* Hypoalbuminemia
* High level of acute phase reactant
* Abnormal liver function tests

* Prior intestinal surgery
* Malabsorption
* Crohn's disease
* Malignancy
* Peripheral edema
* Muscle atrophy

* Surgical bowel resection

* Clinical diagnosis following bowel resection

Radiation enteritis | \+  | \+  | \+  | \+  | \+  | –  | \+  | \+  |

* Abdominal tenderness

| \+  | \+  | –  | Nl  |

* Positive fecal fat

| Nl  | ↓  | Nl  |

* Vitamin B12 deficiency
* Hypoalbuminemia

* Prior history of malignancy and radiation therapy
* Malabsorption
* Telangiectasias

* Radiation

* Segmental bowel inflammation on endoscopy or colonoscopy

Dumping syndrome | –  | \+  | \+  | –  | \+  | –  | –  | \+  |

* Hyperactive bowel sound

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  |

* Hypoglycemia
* Hydrogen breath test

* Malnutrition
* Fat soluble vitamin deficiency

* Postgastrectomy

* Clinical diagnosis following gastrectomy

Others  | 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
Abetalipoproteinemia | –  | \+  | \+  | –  | \+  | –  | \+  | \+  |

* Abdominal distension

| –  | –  | –  | Nl  | –  | Nl  | Nl  | Nl  |

* Low triglyceride
* Low total cholesterol levels
* Acanthocytes
* Low vitamin E levels

* Ataxia
* Visual field defect
* Dysarthria

* Autosomal recessive disorder caused by mutations encoding the microsomal triglyceride transfer protein (MTP)

* Clinical findings and low triglyceride and cholesterol level

Hyperthyroidism | –  | \+  | \+  | –  | –  | ±  | \+  | \+  | –  | –  | –  | –  | Nl  |

* Positive fecal fat

| Nl  | Nl  | Nl  |

* Elevated T4
* Elevated T3
* Decreased TSH
* High serum alkaline phosphatase

* Lump in the neck
* Lid lag
* Malabsorption
* Sweating
* Hyperpigmentation
* Proptosis
* Tremor
* Increased DTR

* Graves' disease
* Hashimoto's thyroiditis
* Toxic adenoma

* TSH

Diabetic neuropathy | –  | \+  | \+  | –  | \+  | –  | \+  | \+  |

* Fecal incontinence

| –  | –  | –  | Nl  |

* Positive fecal fat

| Nl  | ↓  | Nl  |

* Hyperglycemia
* Azotemia
* Hypokalemia

* Malabsorption

* Unclear
* Disordered motility
* Increased intestinal secretion
* Small intestinal bacterial overgrowth

* Clinical diagnosis in a patient with long lasting diabetes mellitus

Systemic sclerosis | –  | \+  | \+  | ±  | \+  | –  | \+  | \+  |

* Epigastric tenderness
* Fecal incontinence

| –  | \+  | –  | Nl  |

* Positive fecal fat

| Nl  | ↓  | Nl  |

* Anti–topoisomerase I (Scl‑70) antibodies
* Antinuclear antibodies (ANA)
* Anti–centromere antibodies
* Anti–RNA polymerase III antibody

* Malabsorption
* Skin changes
* Raynaud phenomenon
* Pulmonary hypertension
* Arthritis
* Telangiectasia
* Chronic renal failure

* Autoimmune reaction

* Clinical diagnosis
* Followed by serologic tests

## Related Chapters

[edit | edit source]

* Constipation
* Gastroenteritis

## References

[edit | edit source]

1. ↑ Casburn-Jones, Anna C; Farthing, Michael Jg (2004). "Traveler's diarrhea". Journal of Gastroenterology and Hepatology. 19 (6): 610–618. doi:10.1111/j.1440-1746.2003.03287.x. ISSN 0815-9319.
2. ↑ Kamat, Deepak; Mathur, Ambika (2006). "Prevention and Management of Travelers' Diarrhea". Disease-a-Month. 52 (7): 289–302. doi:10.1016/j.disamonth.2006.08.003. ISSN 0011-5029.
3. ↑ Pfeiffer, Margaret L.; DuPont, Herbert L.; Ochoa, Theresa J. (2012). "The patient presenting with acute dysentery – A systematic review". Journal of Infection. 64 (4): 374–386. doi:10.1016/j.jinf.2012.01.006. ISSN 0163-4453.
4. ↑ Barr W, Smith A (2014). "Acute diarrhea". Am Fam Physician. 89 (3): 180–9. PMID 24506120.
5. ↑ Amil Dias J (2017). "Celiac Disease: What Do We Know in 2017?". GE Port J Gastroenterol. 24 (6): 275–278. doi:10.1159/000479881. PMID 29255768.
6. ↑ Kotloff KL, Riddle MS, Platts-Mills JA, Pavlinac P, Zaidi A (2017). "Shigellosis". Lancet. doi:10.1016/S0140-6736(17)33296-8. PMID 29254859. Vancouver style error: initials (help)
7. ↑ Yamamoto-Furusho, J.K.; Bosques-Padilla, F.; de-Paula, J.; Galiano, M.T.; Ibañez, P.; Juliao, F.; Kotze, P.G.; Rocha, J.L.; Steinwurz, F.; Veitia, G.; Zaltman, C. (2017). "Diagnóstico y tratamiento de la enfermedad inflamatoria intestinal: Primer Consenso Latinoamericano de la Pan American Crohn's and Colitis Organisation". Revista de Gastroenterología de México. 82 (1): 46–84. doi:10.1016/j.rgmx.2016.07.003. ISSN 0375-0906.
8. ↑ Borbély, Yves M; Osterwalder, Alice; Kröll, Dino; Nett, Philipp C; Inglin, Roman A (2017). "Diarrhea after bariatric procedures: Diagnosis and therapy". World Journal of Gastroenterology. 23 (26): 4689. doi:10.3748/wjg.v23.i26.4689. ISSN 1007-9327.
9. ↑ Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O'Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K. (2017). "Rotavirus infection". Nature Reviews Disease Primers. 3: 17083. doi:10.1038/nrdp.2017.83. ISSN 2056-676X.
10. ↑ Kist M (2000). "[Chronic diarrhea: value of microbiology in diagnosis]". Praxis (Bern 1994) (in German). 89 (39): 1559–65. PMID 11068510.CS1 maint: Unrecognized language (link)
11. ↑ Guerrant RL, Shields DS, Thorson SM, Schorling JB, Gröschel DH (1985). "Evaluation and diagnosis of acute infectious diarrhea". Am. J. Med. 78 (6B): 91–8. PMID 4014291.
12. ↑ López-Vélez R, Turrientes MC, Garrón C, Montilla P, Navajas R, Fenoy S, del Aguila C (1999). "Microsporidiosis in travelers with diarrhea from the tropics". J Travel Med. 6 (4): 223–7. PMID 10575169.
13. ↑ Wahnschaffe, Ulrich; Ignatius, Ralf; Loddenkemper, Christoph; Liesenfeld, Oliver; Muehlen, Marion; Jelinek, Thomas; Burchard, Gerd Dieter; Weinke, Thomas; Harms, Gundel; Stein, Harald; Zeitz, Martin; Ullrich, Reiner; Schneider, Thomas (2009). "Diagnostic value of endoscopy for the diagnosis of giardiasis and other intestinal diseases in patients with persistent diarrhea from tropical or subtropical areas". Scandinavian Journal of Gastroenterology. 42 (3): 391–396. doi:10.1080/00365520600881193. ISSN 0036-5521.
14. ↑ Mena Bares LM, Carmona Asenjo E, García Sánchez MV, Moreno Ortega E, Maza Muret FR, Guiote Moreno MV, Santos Bueno AM, Iglesias Flores E, Benítez Cantero JM, Vallejo Casas JA (2017). "75SeHCAT scan in bile acid malabsorption in chronic diarrhoea". Rev Esp Med Nucl Imagen Mol. 36 (1): 37–47. doi:10.1016/j.remn.2016.08.005. PMID 27765536.
15. ↑ Gibson RJ, Stringer AM (2009). "Chemotherapy-induced diarrhoea". Curr Opin Support Palliat Care. 3 (1): 31–5. doi:10.1097/SPC.0b013e32832531bb. PMID 19365159.
16. ↑ Abraham BP, Sellin JH (2012). "Drug-induced, factitious, & idiopathic diarrhoea". Best Pract Res Clin Gastroenterol. 26 (5): 633–48. doi:10.1016/j.bpg.2012.11.007. PMID 23384808.
17. ↑ Reintam Blaser A, Deane AM, Fruhwald S (2015). "Diarrhoea in the critically ill". Curr Opin Crit Care. 21 (2): 142–53. doi:10.1097/MCC.0000000000000188. PMID 25692805.
18. ↑ McMahan ZH, DuPont HL (2007). "Review article: the history of acute infectious diarrhoea management--from poorly focused empiricism to fluid therapy and modern pharmacotherapy". Aliment. Pharmacol. Ther. 25 (7): 759–69. doi:10.1111/j.1365-2036.2007.03261.x. PMID 17373914.
19. ↑ Schiller LR (2012). "Definitions, pathophysiology, and evaluation of chronic diarrhoea". Best Pract Res Clin Gastroenterol. 26 (5): 551–62. doi:10.1016/j.bpg.2012.11.011. PMID 23384801.
20. ↑ Giannella RA (1986). "Chronic diarrhea in travelers: diagnostic and therapeutic considerations". Rev. Infect. Dis. 8 Suppl 2: S223–6. PMID 3523719.
21. ↑ Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR; et al. (2005). "Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology". Can J Gastroenterol. 19 Suppl A: 5A–36A. PMID 16151544.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
22. ↑ Sauter GH, Moussavian AC, Meyer G, Steitz HO, Parhofer KG, Jüngst D (2002). "Bowel habits and bile acid malabsorption in the months after cholecystectomy". Am J Gastroenterol. 97 (7): 1732–5. doi:10.1111/j.1572-0241.2002.05779.x. PMID 12135027.CS1 maint: Multiple names: authors list (link)
23. ↑ Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R; et al. (1991). "Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia". Gastroenterology. 100 (2): 359–69. PMID 1702075.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
24. ↑ RUBIN CE, BRANDBORG LL, PHELPS PC, TAYLOR HC (1960). "Studies of celiac disease. I. The apparent identical and specific nature of the duodenal and proximal jejunal lesion in celiac disease and idiopathic sprue". Gastroenterology. 38: 28–49. PMID 14439871.CS1 maint: Multiple names: authors list (link)
25. ↑ Konvolinka CW (1994). "Acute diverticulitis under age forty". Am J Surg. 167 (6): 562–5. PMID 8209928.
26. ↑ Satsangi J, Silverberg MS, Vermeire S, Colombel JF (2006). "The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications". Gut. 55 (6): 749–53. doi:10.1136/gut.2005.082909. PMC 1856208. PMID 16698746.CS1 maint: Multiple names: authors list (link)
27. ↑ Haque R, Huston CD, Hughes M, Houpt E, Petri WA (2003). "Amebiasis". N Engl J Med. 348 (16): 1565–73. doi:10.1056/NEJMra022710. PMID 12700377.CS1 maint: Multiple names: authors list (link)
28. ↑ Hertzler SR, Savaiano DA (1996). "Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance". Am J Clin Nutr. 64 (2): 232–6. PMID 8694025.
29. ↑ Briet F, Pochart P, Marteau P, Flourie B, Arrigoni E, Rambaud JC (1997). "Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?". Gut. 41 (5): 632–5. PMC 1891556. PMID 9414969.CS1 maint: Multiple names: authors list (link)
30. ↑ BLACK-SCHAFFER B (1949). "The tinctoral demonstration of a glycoprotein in Whipple's disease". Proc Soc Exp Biol Med. 72 (1): 225–7. PMID 15391722.