Crohn's disease differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Crohn's disease should be differentiated from other causes of diarrhea. It is very important to differentiate it from ulcerative colitis as the management of both conditions is different though the initial presentation may be confused for any of these disorders.[1][2]

Differentiating Crohn's Disease from other Diseases

Differentiating Crohn's Disease from ulcerative colitis

The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.[1][2][3][4][5][6]

Comparisons of various factors in Crohn's disease and ulcerative colitis
Crohn's disease Ulcerative colitis
Terminal ileum involvement Commonly Seldom
Colon involvement Usually Always
Rectum involvement Seldom Usually[7]
Involvement around the anus Common[8] Seldom
Bile duct involvement No increase in rate of primary sclerosing cholangitis Higher rate[9]
Distribution of Disease Patchy areas of inflammation (Skip lesions) Continuous area of inflammation[7]
Endoscopy Deep geographic and serpiginous (snake-like) ulcers Continuous ulcer
Depth of inflammation May be transmural, deep into tissues[8] Shallow, mucosal
Fistulae Common[8] Seldom
Stenosis Common Seldom
Autoimmune disease Widely regarded as an autoimmune disease No consensus
Cytokine response Associated with Th1 Vaguely associated with Th2
Granulomas on biopsy Can have granulomas[8] Granulomas uncommon[7]
Surgical cure Often returns following removal of affected part Usually cured by removal of colon
Smoking Higher risk for smokers Lower risk for smokers[7]
Risk of Cancer Lower than UC Higher

Differentiating Crohn's from other causes of Gastroenteritis

Organism Age predilection Travel History Incubation Size (cell) Incubation Time History and Symptoms Diarrhea type∞ Food source Specific consideration
Fever N/V Cramping Abd Pain Small Bowel Large Bowel Inflammatory Non-inflammatory
Viral Rotavirus <2 y - <102 <48 h + + - + + - Mostly in day cares, most common in winter.
Norovirus Any age - 10 -103 24-48 h + + + + + - Most common cause of gastroenteritis, abdominal tenderness,
Adenovirus <2 y - 105 -106 8-10 d + + + + + - No seasonality
Astrovirus <5 y - 72-96 h + + + + + Seafood Mostly during winter
Bacterial Escherichia coli ETEC Any age + 108 -1010 24 h - + + + + - Causes travelers diarrhea, contains heat-labile toxins (LT) and heat-stable toxins (ST)
EPEC <1 y - 10 6-12 h - + + + + Raw beef and chicken -
EIEC Any ages - 10 24 h + + + + + Hamburger meat and unpasteurized milk Similar to shigellosis, can cause bloody diarrhea
EHEC Any ages - 10 3-4 d - + + + + Undercooked or raw hamburger (ground beef)  Known as E. coli O157:H7, can cause HUS/TTP.
EAEC Any ages + 1010 8-18 h - - + + + - May cause prolonged or persistent diarrhea in children
Salmonella sp. Any ages + 1 6 to 72 h + + + + + Meats, poultry, eggs, milk and dairy products, fish, shrimp, spices, yeast, coconut, sauces, freshly prepared salad. Can cause salmonellosis or typhoid fever.
Shigella sp. Any ages - 10 - 200 8-48 h + + + + + Raw foods, for example, lettuce, salads (potato, tuna, shrimp, macaroni, and chicken) Some strains produce enterotoxin and Shiga toxin similar to those produced by E. coli O157:H7
Campylobacter sp. <5 y, 15-29 y - 104 2-5 d + + + + + Undercooked poultry products, unpasteurized milk and cheeses made from unpasteurized milk, vegetables, seafood and contaminated water. May cause bacteremia, Guillain-Barré syndrome (GBS), hemolytic uremic syndrome (HUS) and recurrent colitis
Yersinia enterocolitica <10 y - 104 -106 1-11 d + + + + + Meats (pork, beef, lamb, etc.), oysters, fish, crabs, and raw milk. May cause reactive arthritis; glomerulonephritis; endocarditis; erythema nodosum.

can mimic appendicitis and mesenteric lymphadenitis.

Clostridium perfringens Any ages > 106 16 h - - + + + Meats (especially beef and poultry), meat-containing products (e.g., gravies and stews), and Mexican foods. Can survive high heat,
Vibrio cholerae Any ages - 106-1010 24-48 h - + + + + Seafoods, including molluscan shellfish (oysters, mussels, and clams), crab, lobster, shrimp, squid, and finfish. Hypotension, tachycardia, decreased skin turgor. Rice-water stools
Parasites Protozoa Giardia lamblia 2-5 y + 1 cyst 1-2 we - - + + + Contaminated water May cause malabsorption syndrome and severe weight loss
Entamoeba histolytica 4-11 y + <10 cysts 2-4 we - + + + + Contaminated water and raw foods May cause intestinal amebiasis and amebic liver abscess
Cryptosporidium parvum Any ages - 10-100 oocysts 7-10 d + + + + + Juices and milk May cause copious diarrhea and dehydration in patients with AIDS especially with 180 > CD4
Cyclospora cayetanensis Any ages + 10-100 oocysts 7-10 d - + + + + Fresh produce, such as raspberries, basil, and several varieties of lettuce. More common in rainy areas
Helminths Trichinella spp Any ages - Two viable larvae (male and female) 1-4 we - + + + + Undercooked meats More common in hunters or people who eat traditionally uncooked meats
Taenia spp Any ages - 1 larva or egg 2-4 m - + + + + Undercooked beef and pork Neurocysticercosis: Cysts located in the brain may be asymptomatic or seizures, increased intracranial pressure, headache.
Diphyllobothrium latum Any ages - 1 larva 15 d - - - + + Raw or undercooked fish. May cause vitamin B12 deficiency



Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient's immunity system.

Cause Osmotic gap History Physical exam Gold standard Treatment
< 50 mOsm per kg > 50 mOsm per kg*
Watery Secretory Crohns + -
Hyperthyroidism + -
VIPoma + -
  • Elevated VIP levels
  • Followed by imaging
Osmotic Lactose intolerance - +
Celiac disease - +
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:

  • Onset associated with change in frequency of stool
  • Onset associated with change in appearance of stool

History of straining is also common

Template:WikiDoc Sources

Differential Diagnosis

Crohn's disease must be differentiated from:[10][11][12][13][14][15][16][17][18]

Disease Cause Symptoms Diagnosis Other findings
Pain Nausea

&

Vomiting

Heartburn Belching or

Bloating

Weight loss Loss of

Appetite

Stools Endoscopy findings
Location Aggravating Factors Alleviating Factors
Acute gastritis Food Antacids ? ? ? - ? Black stools -
Chronic gastritis Food Antacids ? ? ? ? ? - H. pylori gastritis

Lymphocytic gastritis

  • Enlarged folds
  • Aphthoid erosions
-
Atrophic gastritis Epigastric pain - - ? - ? ? - H. pylori

Autoimmune

Autoimmune gastritis diagnosis include:

Crohn's disease - - - - - ? ?
  • Mucosal nodularity with cobblestoning
  • Multiple aphthous ulcers
  • Linier or serpiginous ulcerations
  • Thickened antral folds
  • Antral narrowing
  • Hypoperistalsis
  • Duodenal strictures
GERD
  • Lower esophageal sphincter abnormalities
  • Spicy food
  • Tight fitting clothing
?

(Suspect delayed gastric emptying)

? - - - - Other symptoms:

Complications

Peptic ulcer disease
Duodenal ulcer
  • Pain aggravates with empty stomach

Gastric ulcer

  • Pain aggravates with food
  • Pain alleviates with food
? ? - - - Gastric ulcers
  • Discrete mucosal lesions with a punched-out smooth ulcer base with whitish fibrinoid base
  • Most ulcers are at the junction of fundus and antrum
  • 0.5-2.5cm

Duodenal ulcers

Other diagnostic tests
Gastrinoma - - ?

(suspect gastric outlet obstruction)

? - - - Useful in collecting the tissue for biopsy

Diagnostic tests

Gastric Adenocarcinoma - - ? ? ? ? ? Esophagogastroduodenoscopy
  • Multiple biopsies are taken to establish the diagnosis
Other symptoms
Primary gastric lymphoma - - - - - ? - - Useful in collecting the tissue for biopsy Other symptoms

Oral Crohn's lesions must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.

Disease Presentation Risk Factors Diagnosis Affected Organ Systems Important features Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis
  • Denture users
  • As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication.
  • Clinical diagnosis
  • Confirmatory tests rarely needed
Localized candidiasis

Invasive candidasis

Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions
  • Stress
  • Recent URTI
  • Female sex
  • The symptoms of primary HSV infection generally resolve within two weeks
Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers
  • Painful, red spot or bump that develops into an open ulcer
  • Physical examination
  • Diagnosis of exclusion
  • Oral cavity
  • Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks
Apthous ulcer on the lower surface of the tongue - By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma
Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia
  • Vulvar lesions occur independent of oral lesions
Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma
Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots
Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome
Torus palatinus
Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease
Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease
Agranulocytosis
Syphilis[21]
oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus
  • Symptomatic treatment
Coxsackie virus stomatitis - Adapted from Dermatology Atlas.[22]
Chicken pox
Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles
  • Unvaccinated individuals[23][24]
  • Crowded and/or unsanitary conditions
  • Traveling to less developed and developing countries
  • Immunocompromized
  • Winter and spring seasons
  • Born after 1956 and never fully vaccinated
  • Health care workers
Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483


Crohn's disease must be differentiated from diseases that cause abdominal pain and chronic diarrhea. The table below summarizes the findings that differentiate watery causes of chronic diarrhea:[25][26][27][28][29]

Cause Osmotic gap History Physical exam Gold standard for diagnosis
< 50 mOsm per kg > 50 mOsm per kg*
Zollinger-Ellison syndrome + - Gastrin levels
Crohn's disease + -
Hyperthyroidism + -
VIPoma + -
  • Elevated VIP levels
  • Followed by imaging
Lactose intolerance - +
Celiac disease - +
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:

  • Onset associated with change in frequency of stool
  • Onset associated with change in appearance of stool

History of straining is also common.


References

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  4. Karolewska-Bochenek K, Dziekiewicz M, Banaszkiewicz A (2017). "Budesonide MMX in pediatric patients with ulcerative colitis". J Crohns Colitis. doi:10.1093/ecco-jcc/jjx069. PMID 28505293.
  5. Silva M, Cardoso H, Macedo G (2017). "Patency Capsule Safety in Crohn's Disease". J Crohns Colitis. doi:10.1093/ecco-jcc/jjx064. PMID 28486597.
  6. Stidham RW, Cross RK (2016). "Endoscopy and cross-sectional imaging for assessing Crohn׳s disease activity". Tech Gastrointest Endosc. 18 (3): 123–130. doi:10.1016/j.tgie.2016.08.001. PMC 5405438. PMID 28458507.
  7. 7.0 7.1 7.2 7.3 Kornbluth, Asher (2004). "Ulcerative Colitis Practice Guidelines in Adults" (PDF). American Journal of Gastroenterology. 99 (7): 1371–1385. doi:10.1111/j.1572-0241.2004.40036.x. PMID 15233681. Retrieved 2006-11-08. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
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  9. Broomé, Ulrika (2006). "Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer". Seminars in Liver Disease. 26 (1): 31–41. doi:10.1055/s-2006-933561. PMID 16496231. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
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  11. Sipponen P, Maaroos HI (2015). "Chronic gastritis". Scand J Gastroenterol. 50 (6): 657–67. doi:10.3109/00365521.2015.1019918. PMC 4673514. PMID 25901896.
  12. Sartor RB (2006). "Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis". Nat Clin Pract Gastroenterol Hepatol. 3 (7): 390–407. doi:10.1038/ncpgasthep0528. PMID 16819502.
  13. Sipponen P (1989). "Atrophic gastritis as a premalignant condition". Ann Med. 21 (4): 287–90. PMID 2789799.
  14. Badillo R, Francis D (2014). "Diagnosis and treatment of gastroesophageal reflux disease". World J Gastrointest Pharmacol Ther. 5 (3): 105–12. doi:10.4292/wjgpt.v5.i3.105. PMC 4133436. PMID 25133039.
  15. Ramakrishnan K, Salinas RC (2007). "Peptic ulcer disease". Am Fam Physician. 76 (7): 1005–12. PMID 17956071.
  16. Banasch M, Schmitz F (2007). "Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors". Wien Klin Wochenschr. 119 (19–20): 573–8. doi:10.1007/s00508-007-0884-2. PMID 17985090.
  17. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM (2005). "Gastric adenocarcinoma: review and considerations for future directions". Ann Surg. 241 (1): 27–39. PMC 1356843. PMID 15621988.
  18. Ghimire P, Wu GY, Zhu L (2011). "Primary gastrointestinal lymphoma". World J Gastroenterol. 17 (6): 697–707. doi:10.3748/wjg.v17.i6.697. PMC 3042647. PMID 21390139.
  19. Ann M. Gillenwater, Nadarajah Vigneswaran, Hanadi Fatani, Pierre Saintigny & Adel K. El-Naggar (2013). "Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic entity!". Advances in anatomic pathology. 20 (6): 416–423. doi:10.1097/PAP.0b013e3182a92df1. PMID 24113312. Unknown parameter |month= ignored (help)
  20. Andrès E, Zimmer J, Affenberger S, Federici L, Alt M, Maloisel F. (2006). "Idiosyncratic drug-induced agranulocytosis: Update of an old disorder". Eur J Intern Med. 17 (8): 529–35. Text "pmid 17142169" ignored (help)
  21. title="By Internet Archive Book Images [No restrictions], via Wikimedia Commons" href="https://commons.wikimedia.org/wiki/File:A_manual_of_syphilis_and_the_venereal_diseases%2C_(1900)_(14595882378).jpg"
  22. "Dermatology Atlas".
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  29. 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.