• Sign Up

Crohn Disease

Crohn Disease

Article Author:
Indika Ranasinghe
Article Editor:
Ronald Hsu
6/9/2020 5:19:53 PM
For CME on this topic:
Crohn Disease CME
PubMed Link:
Crohn Disease


Crohn disease (CD) and ulcerative colitis (UC) are two conditions commonly referred to as inflammatory bowel disease (IBD). They are immunologically mediated inflammatory diseases of the gastrointestinal tract. In CD, the inflammation extends through the entire thickness of the bowel wall from the mucosa to the serosa. The disease runs a relapsing and remitting course. With multiple relapses, CD can progress from an initially mild to moderate inflammatory conditions to severe penetrating (fistulization) and/or stricturing disease.[1][2][3][4][5]

Crohn disease can affect any part of the gastrointestinal tract.About1/3rd of patients have small bowel involvement, especially the terminal ileum, another 20% have only colon involvement and about 50% have involvement of both the colon and small bowel.

There is no cure and most patients experience bouts of remissions and relapse at unpredictable times. This disease leads to very poor quality of life.


Although the exact etiology of inflammatory bowel disease (IBD) is not known, there is substantial evidence to suggest that the disease is resulting from an inappropriate immune response in the bowel to situations from environmental factors such as drugs, toxins, infections or intestinal microbes in a genetically susceptible host. More than a hundred genes associated with IBD have been identified. In Crohn's disease particularly, there appears to be a genetic association with phenotypes. Specifically, NOD2/CARD15 mutations were found to be associated with a phenotype of Crohn's disease which was associated in those diagnosed at a younger age, with ileal involvement, increased severity of ileal disease requiring surgical intervention/reoperation. In the future, this genotyping could potentially provide prognostic information on the severity of the disease. Furthermore, it could predict which patient's should be considered for surgical management vs. medical management based on a more detailed understanding of genetic analysis.[6]


Crohn's disease (CD) is most commonly seen in the western developed world in North America, northern Europe, and New Zealand. Its incidence has a bimodal distribution with the onset occurring most frequently between ages 15 to 30 years and 40 to 60 years old. It is more prominent in urban than rural areas. There is a high incidence in Northern Europeans and Jewish descent (incidence 3.2/1000) contrasting to a significant infrequent prevalence in Asians, Africans, and South Americans.[7] However, recent studies have shown a significant increase in incidence in rapidly industrializing areas of Asia, Africa, and Australasia.[8]


The pathophysiology is multifactorial and involves genetic predisposition, infectious, immunological, environmental, and dietary. The characteristic transmural inflammation can include the entire GI tract from mouth to the perianal area; although most frequently involve terminal ileum and right colon. The initial lesion starts out as an infiltrate around an intestinal crypt. This goes on to develop ulceration first in the superficial mucosa and involves to deeper layers. As the inflammation progresses, non-caseating granulomas form involving all layers of the intestinal wall. It can develop into the classic cobblestone mucosal appearances and skip lesions along the length of the intestine sparing areas with normal mucosa. As the flare of Crohn's settles, scarring replaces the inflamed areas of the intestines.[9]

Granuloma formation is very common in Crohn disease but their absence does not exclude the diagnosis. The ongoing inflammation and scarring lead to bowel obstruction and stricture formation. 

Finally, Crohn disease is also associated with enterovesical, enteroenteral, enterocutaneous and enterovaginal fistulas.


The immune-mediated response in Crohn's disease involves both innate and acquired mechanisms by macrophages, neutrophils, and T-cells in the intestine which promote pro-inflammatory mediators like TNF-alpha. Colonic Crohn's lesions were found to have high levels of cytokines like IFN-gamma, IL-2, IL-12, and IL-18. Crohn's disease is primarily regulated by TH1 and TH17 mediated processes.[10]

History and Physical

Patients with flare-ups of Crohn's disease typically presents with abdominal pain (right lower quadrant), flatulence/bloating, diarrhea (can include mucus and blood), fever, weight loss, anemia.

In severe cases, perianal abscess, perianal Crohn's disease, and cutaneous fistulas can be seen.

When the small bowel is involved, it may present with diarrhea, malabsorption, weight loss, abdominal pain, and anorexia. Enterovesical fistulae may present with pneumaturia, recurrent urinary tract infections, and feculent vaginal discharge.

Crohn's disease is associated with extraintestinal manifestations including episcleritis, uveitis, stomatitis, aphthous ulcers, liver steatosis, gallstones, cholangitis, primary sclerosing cholangitis, nephrolithiasis, hydronephrosis, urinary tract infections, arthritis (spine - sacral, knee, ankles, hips, wrist, elbows), ankylosing spondylitis, erythema nodosum, and pyoderma gangrenosum.[11]

Thromboembolic disease is now recognized to be a common complication of Crohn disease. IT may present with deep vein thrombosis, stroke or pulmonary embolism.

The perineum must be examined in all patients. The inspection may reveal skin tags, ulcers, fistulas, scarring, and abscess. Frank perforation is rare but can be a presentation of Crohn disease. Finally, colon cancer is another complication of Crohn disease.


Stool tests to rule out infections include culture and sensitivities, ovum and parasites, Clostridium difficile toxins, leukocyte count.  Stool for calprotectin can detect active CD and also used for monitoring disease.[12][13][14][15]

Blood tests including baseline CBC and a metabolic panel can highlight the presence of anemia (B12  or iron deficiency) or liver disease. Special serology such as normal anti-neutrophil cytoplasmic antibodies (ANCA) and raised anti-saccharomyces cerevisiae antibodies (ASCA) can distinguish Crohn's disease from ulcerative colitis. C-reactive protein (CRP) or sedimentary rate (ESR) can reflect the severity of the inflammation.

CT scan/MRE of the abdomen and pelvis can detect abscesses and fistulization. The choice between CT or MR enterography is largely directed at minimizing radiation exposure in younger populations. Both give a higher definition of the diseased intestine. However, MRI can provide more detail when investigating the fistulizing disease. The use of video capsule endoscopy (VCE) can visualize the small bowel for CD when regular endoscopy or colonoscopy cannot reach to visualize these areas. Capsule endoscopy can only detect mucosal changes, whereas MRI can detect transmural inflammation and also identify other complications.

Plain x-rays are ordered when bowel obstruction is suspected.

Small bowel follow-through is often used to assess the involvement of the terminal ileum and can also detect fistulas. The classic string sign due to stricture formation or spasm is often seen.

For those patients too ill to undergo colonoscopy or CT scan, nuclear imaging may reveal sites of inflammation.

Before initiation of any treatment, vaccination history (tetanus, diphtheria, pertussis, HPV, influenza, pneumococcal, hepatitis A, hepatitis B, MMR, VZV) should be known, if no prior history titers of MMR, VZV, and hepatitis A/B should be checked. Baseline PPD with CXR should also be checked before any treatment. Baseline thiopurine methyltransferase (TPMT) levels should be checked before deciding on treatment options. Low levels of TMPT may result in an increased risk of side effects, whereas very high levels may decrease the effectiveness of prescribed treatment.

Treatment / Management

The medical treatment is broadly grouped into two classes:

  • Mild to moderate disease can be treated by oral mesalamine, immunomodulators such as thiopurines (mercaptopurines, azathioprine), methotrexate, and steroids.
  • Moderate to severe disease (including fistulizing disease) will be best treated using a combination of immunomodulators and biologics (infliximab, adalimumab, golimumab, vedolizumab) or biologics alone.[10]

Biologics are immunoglobulins engineered to direct against specific cytokines or receptors involving in the inflammation process. Each biologic agent works against one specific site at a molecular level. Anti-tumor necrosis factor (TNF) alpha is a monoclonal antibody that can block the TNF in the circulation from their inflammatory actions. Anti-integrin agents are adhesion molecule inhibitors that bind the subunits of the MAdCAM receptors of the endothelial cells at the inflammatory sites. They halt the trafficking of lymphocytes from the circulation into the wall of the intestine, thereby stopping the inflammatory response targeted at the bowel.  Examples of anti-TNF agents are infliximab, adalimumab, golimumab. Examples of adhesion molecule inhibitors are natalizumab, vedolizumab. Vedolizumab is gut-specific and has less systemic side effects. Many newer therapeutic agents for inflammatory bowel disease are in the pipeline.

Surgical treatments are used for complications such as bowel obstructions, abscess, fistulas, or perforated bowel.

Dietician input and nutritional supplementation are highly recommended before and during treatment of Crohn's disease.[16][17][18][19]


  1. Fecal calprotectin may help differentiate between IBD and IBS
  2. Chromoendoscopy  should be utilized during colonoscopy as it may increase diagnostic yield for colorectal dysplasia
  3. Avoid NSAIDs as they may exacerbate disease
  4. Avoid smoking
  5. Get mental health counseling as many patients develop depression
  6. Sulfasalazine is effective for mild disease
  7. Controlled ileal release budesonide can be used for induction of remission in patients with moderate ileocecal disease
  8. Avoid the use of metronidazole as it is ineffective in Crohn disease
  9. Mild diarrhea can be managed with antidiarrheals
  10. Thiopurines can be used for steroid-sparing
  11. Anti TNFs can be used in patients resistant to steroids
  12. Drain abscess radiologically if possible

Differential Diagnosis

  • Amebiasis
  • Behcet disease
  • Celiac disease
  • Intestinal carcinoid
  • Intestinal tuberculosis
  • Mesenteric ischemia
  • Ulcerative colitis


Crohn disease is a chronic inflammatory disorder with no cure. Despite optimal therapy, most patients have a poor quality of life. The life expectancy is slightly reduced to the development of malignancies, genitourinary disease, liver, and biliary tract complications. The majority of Crohn patients who develop complications need surgery and as the disease progresses, some need multiple procedures. Overall, patients with proximal disease have higher mortality than those with distal disease.

Deterrence and Patient Education

Patients should undergo screening for skin cancers, irrespective of biological therapy.

Bone density should be assessed regularly

Vaccination against pneumococcus, H influenzae, and the flu

Enhancing Healthcare Team Outcomes

Crohn disease is a serious chronic inflammatory disorder that is difficult to diagnose and manage. Besides the GI tract, the disease affects many other organs leading to high morbidity and even premature death. The current consensus is that this disorder should be managed by an interprofessional team dedicated to the management of inflammatory bowel disease.

The diagnosis and management of Crohn disease require an interprofessional that includes a nurse practitioner or physician assistant, internists, hematologist, gastroenterologist, general surgeon, dietitian, stoma nurse, and a pharmacist. The disorder affects many organs in the body and hence the appropriate specialist should be consulted early on in the disease course.

A nurse practitioner or physician assistant should follow the patient throughout the course and monitor the course of the disease. Any change in the symptoms should be immediately reported to the team. A dietitian should educate the patient on foods to eat and what to avoid. A stoma nurse should educate the patient on the cleaning of the skin and managing everyday problems with this method of stool evacuation. 

The pharmacist should educate the patient on the different medications, their benefits, adverse effects and importance of compliance.

Many different clinicians see these patients as they may develop extraintestinal problems. The patient should be urged to undergo tests to screen for skin and colon malignancies. Finally, most patients develop depression and severe anxiety and hence a mental health nurse should provide continuous counseling.

The disorder is usually managed with medications but complications require surgery. Most patients have relapses and remissions and need life long follow up. The prognosis for most patients with Crohn disease is guarded and the quality of life is poor. [20] AN interprofessional team approach can optimize outcomes within the limitations of the condition. [Level 5]


[1] Lightner AL,McKenna NP,Alsughayer A,Loftus EV Jr,Raffals LE,Faubion WA,Moir C, Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients. Journal of pediatric surgery. 2019 Jan 18;     [PubMed PMID: 30773391]
[2] Marazuela García P,López-Frías López-Jurado A,Vicente Bártulos A, Acute abdominal pain in patients with Crohn's disease: what urgent imaging tests should be done? Radiologia. 2019 Feb 13;     [PubMed PMID: 30772003]
[3] Aksan A,Farrag K,Stein J, An update on the evaluation and management of iron deficiency anemia in inflammatory bowel disease. Expert review of gastroenterology     [PubMed PMID: 30791779]
[4] Hwang JH,Yu CS, Depression and resilience in ulcerative colitis and Crohn's disease patients with ostomy. International wound journal. 2019 Mar;     [PubMed PMID: 30793856]
[5] Khan S,Rupniewska E,Neighbors M,Singer D,Chiarappa J,Obando C, Real-world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review. Journal of clinical pharmacy and therapeutics. 2019 Mar 14;     [PubMed PMID: 30873648]
[6] Zaidi D,Wine E, Regulation of Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κβ) in Inflammatory Bowel Diseases. Frontiers in pediatrics. 2018;     [PubMed PMID: 30425977]
[7] Ghersin I,Khteeb N,Katz LH,Daher S,Shamir R,Assa A, Trends in the epidemiology of inflammatory bowel disease among Jewish Israeli adolescents: a population-based study. Alimentary pharmacology     [PubMed PMID: 30687945]
[8] Coward S,Clement F,Benchimol EI,Bernstein CN,Avina-Zubieta JA,Bitton A,Carroll MW,Hazlewood G,Jacobson K,Jelinski S,Deardon R,Jones JL,Kuenzig ME,Leddin D,McBrien KA,Murthy SK,Nguyen GC,Otley AR,Panaccione R,Rezaie A,Rosenfeld G,Peña-Sánchez JN,Singh H,Targownik LE,Kaplan GG, Past and Future Burden of Inflammatory Bowel Diseases Based on Modeling of Population-Based Data. Gastroenterology. 2019 Jan 10;     [PubMed PMID: 30639677]
[9] Greuter T,Piller A,Fournier N,Safroneeva E,Straumann A,Biedermann L,Godat S,Nydegger A,Scharl M,Rogler G,Vavricka SR,Schoepfer AM, Upper Gastrointestinal Tract Involvement in Crohn's Disease: Frequency, Risk Factors, and Disease Course. Journal of Crohn's     [PubMed PMID: 30165603]
[10] Targan SR, Biology of inflammation in Crohn's disease: mechanisms of action of anti-TNF-a therapy. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2000 Sep;     [PubMed PMID: 11023555]
[11] Fumery M,Pariente B,Sarter H,Savoye G,Spyckerelle C,Djeddi D,Mouterde O,Bouguen G,Ley D,Peneau A,Dupas JL,Turck D,Gower-Rousseau C, Long-term outcome of pediatric-onset Crohn's disease: A population-based cohort study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018 Dec 23;     [PubMed PMID: 30611597]
[12] Fadeeva NA,Korneeva IA,Knyazev OV,Parfenov AI, Biomarkers of inflammatory bowel disease activity. Terapevticheskii arkhiv. 2018 Dec 30;     [PubMed PMID: 30701842]
[13] Parfenov AI,Knyazev OV,Kagramanova AV,Fadeeva NA, Personalized medicine in the treatment of inflammatory bowel diseases. Terapevticheskii arkhiv. 2018 Feb 15;     [PubMed PMID: 30701765]
[14] Kedia S,Das P,Madhusudhan KS,Dattagupta S,Sharma R,Sahni P,Makharia G,Ahuja V, Differentiating Crohn's disease from intestinal tuberculosis. World journal of gastroenterology. 2019 Jan 28;     [PubMed PMID: 30700939]
[15] Moon JS, Clinical Aspects and Treatments for Pediatric Inflammatory Bowel Diseases. Pediatric gastroenterology, hepatology     [PubMed PMID: 30671373]
[16] Brown SR,Fearnhead NS,Faiz OD,Abercrombie JF,Acheson AG,Arnott RG,Clark SK,Clifford S,Davies RJ,Davies MM,Douie WJP,Dunlop MG,Epstein JC,Evans MD,George BD,Guy RJ,Hargest R,Hawthorne AB,Hill J,Hughes GW,Limdi JK,Maxwell-Armstrong CA,O'Connell PR,Pinkney TD,Pipe J,Sagar PM,Singh B,Soop M,Terry H,Torkington J,Verjee A,Walsh CJ,Warusavitarne JH,Williams AB,Williams GL,Wilson RG, The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2018 Dec;     [PubMed PMID: 30508274]
[17] de Kloet LC,Schagen SEE,van den Berg A,Clement-de Boers A,Houdijk MECAM,van der Kaay DCM, [Growth failure as a symptom of inflammatory bowel disease]. Nederlands tijdschrift voor geneeskunde. 2018 Nov 19;     [PubMed PMID: 30500117]
[18] Rodríguez-Lago I,Ferreiro-Iglesias R,Nos P,Gisbert JP, Management of acute severe ulcerative colitis in Spain: A nationwide clinical practice survey. Gastroenterologia y hepatologia. 2019 Feb;     [PubMed PMID: 30293913]
[19] Ambruzs JM,Larsen CP, Renal Manifestations of Inflammatory Bowel Disease. Rheumatic diseases clinics of North America. 2018 Nov;     [PubMed PMID: 30274631]
[20] Inokuchi T,Takahashi S,Hiraoka S,Toyokawa T,Takagi S,Takemoto K,Miyaike J,Fujimoto T,Higashi R,Morito Y,Nawa T,Suzuki S,Nishimura M,Inoue M,Kato J,Okada H, Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics. Journal of gastroenterology and hepatology. 2019 Feb 6;     [PubMed PMID: 30724387]