Cholera differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Priyamvada Singh, MBBS [2]

## Overview

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Patients with cholera may have a history of consumption of contaminated food or water and/or travel to an endemic area. Symptoms of cholera usually develop within 24-48 hour of infection. Patient presents with sudden-onset, painless, odorless, rice-watery, large-volume stool; abdominal cramps; vomiting; and fever. Cholera should be differentiated from other infectious causes of diarrhea such as rotavirus, E. coli, amoebic dysentry, and giardiasis. Cholera should also be differentiated from some non-infectious causes of diarrhea such as VIPoma, tubulovillous adenoma, and food poisoning.[1][2][3][4]

## Differentiating Cholera from other Diseases

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Cholera must be differentiated from other conditions associated with acute onset diarrhea, including:[1][2][3][4]

### Infectious causes of diarrhea

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* It may be difficult to differentiate cholera from other infectious causes of diarrhea, especially if it is mild and in early stages.
* Fresh stool microscopy, stool culture, PCR, and other techniques help to differentiate these conditions. Stool tests are useful, cheap, and frequently used to differentiate cholera from other infectious conditions. Other tests (e.g., PCR, serotyping), though sensitive and specific, may not be performed due to prohibitive cost or lack of availability at many healthcare centers.

#### Shigella

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* Shigella patients present with acute, bloody diarrhea, whereas cholera patients have watery diarrhea.
* Shigella causes invasive diarrhea and thus presents with symptoms of fever, abdominal cramps, and rectal pain, which are not observed in patients with cholera.
* Vomiting is usually absent in shigella but is frequently seen in cholera.

#### Amoebic Hemorrhagic E. coli Dysentery

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* Bloody diarrhea, which is not seen in cholera, guides clinicians toward a diagnosis of dysentery.
* The volume of stool is not as high as seen in cases of cholera.

#### Giardiasis

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* The volume of stool is not as high as in cases of cholera.
* Stool microscopy is used to detect eggs and parasites.
* The stool of giardiasis patients produces a strong odor, whereas cholera patients usually have odorless stools.

#### Strongyloides

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* The volume of stool is not as high as in cases of cholera.
* Stool microscopy is used to detect eggs and parasites.

#### Food poisoning

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* The volume of stool is not as high as in cases of cholera.

### Non-infectious causes of diarrhea

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#### VIPoma

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* Patients present with a chronic history of diarrhea
* Volume of stool is not as high as in cases of cholera
* Negative stool examination and culture
* Fasting gut hormones confirm the diagnosis

#### Tubulovillous adenoma

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* Colonoscopy and biopsy confirm the diagnosis
* Patients present with a chronic history of diarrhea
* Volume of stool is not as high as in cases of cholera
* Negative stool examination and culture

The table below summarizes the findings that differentiate watery causes of chronic diarrhea[5][6][7][8]

Cause  | Osmotic gap  | History  | Physical exam  | Gold standard  | Treatment

|
|
|
|
|

< 50 mOsm per kg  | > 50 mOsm per kg*
Watery  | Secretory  | Crohns | \+  | \-  |

* Abdominal pain followed by diarrhea

* Abdominal tenderness when palpated in severe disease
* Blood seen on rectal exam
* Fever
* Tachycardia
* Hypotension

* Colonoscopy with biopsy

* Topical mucosamine and corticosteroids are preferred
* Mesalamine and sulfasalazine are used for remission

Hyperthyroidism | \+  | \-  |

* Excessive sweating
* Heat intolerance
* Increased bowel movements

* Lump in the neck
* Proptosis
* Tremors
* Increased DTR

* TSH with T3 and T4

* Carbimazole and methimazole
* Beta blockers like propylthiouracil
* Iodine-131

VIPoma | \+  | \-  |

* Watery diarrhea
* Dehydration (thirst, dry skin, dry mouth, tiredness, headaches, and dizziness)
* Lethargy, muscle weakness
* Nausea, vomiting
* Crampy abdominal pain
* Weight loss
* Flushing

* Tachycardia

* Rash
* Facial flushing
* Abdominal distention
* Abdominal tenderness in the right upper abdominal quadrant

* Elevated VIP levels
* Followed by imaging

* Sandostatin or chemotherapy for malignant tumors
* Surgical removal of the tumor

Osmotic | Lactose intolerance | \-  | \+  |

* Abdominal pain
* Bloating
* Diarrhea
* Flatulence

* Abdominal tenderness

* Intestinal biopsy

* Avoidance of dietary lactose
* Substitution to maintain nutrient intake
* Regulation of calcium intake
* Use of enzyme lactase

Celiac disease | \-  | \+  |

* May be asymptomatic
* Vague abdominal pain
* Diarrhea
* Weight loss
* Malabsorption / steatorrhea
* Bloatedness

* Abdominal pain and cramping
* Abdominal distention
* Tetany
* Mouth ulcers
* Dermatitis herpetiformis
* Signs of the fat-soluble vitamins A, D, E, and K deficiency

* IgA tissue transglutaminase Ab

* Gluten-free diet

| Functional  | Irritable bowel syndrome | \-  | \-  |

Abdominal pain or discomfort recurring at least 3 days per month in the past 3 months and associated with 2 or more of the following:

* Improves with defecation

* Onset associated with change in frequency of stool

* Onset associated with change in appearance of stool

* 25% of bowel movements are loose stools

History of straining is also common

* Abdominal tenderness
* Hard stool in the rectal vault

* Clinical diagnosis
* ROME III criteria
* Pharmacologic studies based criteria

* High dietary fiber
* Osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose
* Antispasmodic drugs (e.g. anticholinergics such as hyoscyamine or dicyclomine)

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## Differential Diagnosis by Organ System

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Cardiovascular | No underlying causes

|

Chemical / poisoning | No underlying causes
Dermatologic | No underlying causes
Drug Side Effect | No underlying causes
Ear Nose Throat | No underlying causes
Endocrine | No underlying causes
Environmental | No underlying causes
Gastroenterologic | VIPoma, Tubulovillous adenoma, Food poisoning
Genetic | No underlying causes
Hematologic | No underlying causes
Iatrogenic | No underlying causes
Infectious Disease | Giardiasis, Amoebic dysentry, E. coli, Strongyloides,
Musculoskeletal / Ortho | No underlying causes
Neurologic | No underlying causes
Nutritional / Metabolic | No underlying causes
Obstetric/Gynecologic | No underlying causes
Oncologic | No underlying causes
Opthalmologic | No underlying causes
Overdose / Toxicity | No underlying causes
Psychiatric | No underlying causes
Pulmonary | No underlying causes
Renal / Electrolyte | No underlying causes
Rheum / Immune / Allergy | No underlying causes
Sexual | No underlying causes
Trauma | No underlying causes
Urologic | No underlying causes
Miscellaneous | No underlying causes

## References

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1. ↑ 1.0 1.1 Sack DA, Sack RB, Nair GB, Siddique AK (2004). "Cholera". Lancet. 363 (9404): 223–33. PMID 14738797.CS1 maint: Multiple names: authors list (link)
2. ↑ 2.0 2.1 Krejs GJ (1987). "VIPoma syndrome". Am J Med. 82 (5B): 37–48. PMID 3035922.
3. ↑ 3.0 3.1 Guerrant RL, Van Gilder T, Steiner TS, et al.; Infectious Diseases Society of America. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32(3):331–351.
4. ↑ 4.0 4.1 Scallan, Elaine, et al. "Foodborne illness acquired in the United States—unspecified agents." Emerg Infect Dis 17.1 (2011): 16-22.
5. ↑ 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)
6. ↑ 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)
7. ↑ 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)
8. ↑ 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)

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