Crohn's disease - Clinical review

Diagnosing and managing this inflammatory bowel disease.

Representation of an endoscopic image of the intestine affected by Crohn's disease
Representation of an endoscopic image of the intestine affected by Crohn's disease

Section 1: Epidemiology and aetiology
Section 2: Making the diagnosis
Section 3: Managing the condition
Section 4: Prognosis
Section 5: Case study
Section 6: Evidence base

Section 1: Epidemiology and aetiology

Crohn’s disease (CD) and ulcerative colitis (UC) are the most common inflammatory bowel (IBD) diseases affecting the gastrointestinal tract. Crohn's disease (CD) is characterised by recurring inflammation and can affect any part of the GI tract from the mouth to the anus.

The inflammation is transmural and can result in strictures, microperforations and fistulae. It may not be contiguous and can result in skip lesions throughout the bowel.

Histologically, CD is characterised by transmural lymphoid aggregates, non-necrotising granulomas, fissuring and microscopic skip lesions. Although granulomas are strongly associated with CD, they are only present in 10% of patients.1

The prevalence of CD in the UK is estimated to be 157 per 100,000 with an annual incidence of 9.56 per 100,000 per year.2 It is estimated that at least 115,000 UK patients currently have the condition. The onset has two age peaks. The first, larger peak is at 15-30 years of age; the second is at 60-80.1,3 

The incidence of recognition of the disease is rapidly increasing in children of all ages with about 30% recognised before the age of 20. The female to male ratio is 1.8:1 in adults and 1.6:1 in children.

The cause of CD is yet to be established. Genetic predisposition and smoking are thought to be the most common contributing factors.4 Although no gene has yet been identified, an increased incidence is seen among first and second-degree relatives.

A disturbance in normal gut flora has been observed, with a reduction in lactobacilli and bifidobacteria and an increase in facultative anaerobes.

Additional purported aetiological considerations include environmental and dietary factors, although no links have been established.5

CD can be classified according to severity (table 1), or by the Montreal classification, which classifies CD according to its predominant phenotypic elements (table 2).6

Table 1: Classification according to severity
Mild to moderate disease Moderate to severe disease Severe to fulminant disease
Patient able to tolerate oral diet without dehydration, abdominal pain, abdominal mass or obstruction Patients with fever, weight loss, abdominal pain, anemia and vomiting without frank obstruction Patients with high fever, persistent vomiting, bowel obstruction and abdominal abscess
Table 2: Montreal classification for Crohn's disease
Age at diagnosis Location of disease Behaviour of disease
A1: Below 16 years L1: Disease isolated to ileum B1: Not causing strictures or perforations
A2: 17-40 years L2: Disease isolated to large bowel B2: Causing strictures
A3: Over 40 years L3: Disease involving ileum and colon B3: Causing perforations

Section 2: Making the diagnosis

Patients with CD may present with acute symptoms or with relapsing chronic features.

Symptoms include diarrhoea, abdominal pain, perianal disease, weight loss, anorexia, malnutrition and non-specific inflammatory symptoms, such as fever and fatigue.

The abdominal pain is usually insidious, commonly in the right lower quadrant, and may be associated with a tender inflammatory mass.

CD affecting the colon can be associated with rectal bleeding, but this is more common in ulcerative colitis (UC). Perianal lesions, including abscesses, fissures and fistulas, are characteristic features of CD.

Recurrent mouth ulcers and stomatitis may also be a feature.

Patients with severe disease may present with extra-intestinal manifestations (table 3).

Presentations in children can be even more non-specific, but unexplained malnutrition, bone demineralisation, delayed growth and puberty may suggest possible CD.

Table 3: Extra intestinal manifestations of Crohn’s disease
Dermatological Skeletal Ophthalmic
Erythema nodosum Large joint arthritis Episcleritis
Pyoderma gangrenosum Sacroilitis Iritis
Granulomatous lesions ankylosing spondylitis

Basic investigations include FBC, biochemistry, LFTs, CRP, ESR and stool culture.

Although raised inflammatory markers are non-specific, high CRP levels are usually indicative of active disease or bacterial complication and can be used to monitor disease progression and treatment.

Serological markers can be used to differentiate CD and UC in the tertiary setting, but their use in diagnosis is yet to be established.7

Anti-Saccharomyces cerevisiae antibodies are more common in CD than UC, and perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are more commonly elevated in UC.

Diagnosis is based on characteristic histological features from biopsies of CD-affected mucosa. With the clinical presentation, this establishes the diagnosis and excludes other causes of intestinal ulceration, such as enteric infections, ischaemia, diverticulitis or NSAID-induced enteropathy.

The gold standard investigation is ileocolonoscopy with biopsies, to define the presence and severity of morphological recurrence and predict the clinical course. This is recommended if recurrence is suspected.

Alternative investigations may be used, particularly if CD is thought to affect the GI tract out of reach of standard colonoscopy, such as the proximal small bowel.

Such investigations include barium follow-through, MR enterography, capsule endoscopy and radionucleotide scans.8

CT scans can be useful in the acute setting to differentiate from other disease processes and identify acute complications, such as bowel obstruction and collections.

For perianal disease, MRI is particularly useful in delineating the presence and complexity of fistulas and abscesses. Anorectal examination under anaesthesia can be diagnostic and therapeutic in anorectal CD.

Section 3: Managing the condition

The aim of management is to treat active disease, reduce recurrence and maintain quality of life.

Owing to the multifactorial consequences of CD, a multidisciplinary approach is essential, involving gastroenterologists, surgeons, pharmacists, dietitians, stoma nurses and psychologists.

Medical management
The aim of medical therapy in CD is to induce and maintain remission (table 4). Most effective for inducing remission are corticosteroids and, in certain cases, infliximab, a monoclonal antibody to TNF-alpha.

Table 4: Medical therapy for Crohn's disease14
Disease severity/ anatomical location Drug
Induction of remission Mild to moderate disease
Ileal/right colon
Prednisolone (oral)
Severe disease Prednisolone (IV)
Maintenance of remission Azathioprine,

Steroids induce remission in 70-80% of cases, but less effectively if only the colon is involved. They are useful for maintaining remission in the short term, but generally should not be used for maintenance.

In moderate to severe disease, steroids are commenced alongside immunomodulatory drugs, usually azathioprine. Once immunosuppression is established, the steroids can be tapered off, usually over weeks or months.

Aminosalicylates (sulfasalazine and 5-aminosalicylic acid) are used to treat mild to moderate disease of the colon and for preventing recurrence after small bowel resection. Budesonide is a topically active corticosteroid acting in the colon and small bowel. While it has fewer systemic side-effects than corticosteroids, it may not be as effective.

Antibiotics (typically metronidazole and ciprofloxacin) have a role in treating perianal disease.

Nutrition management should not be overlooked, particularly in children and young adults in whom there are concerns about growth and the side-effects of steroids.

Infliximab is licensed for patients with active fistulating disease or disease not responding to conventional therapy.9 It is reasonably effective at inducing remission, but less so at maintaining it, and has a poor cost-benefit ratio and concerns regarding long-term side-effects.10

It should be given as a planned course until disease is controlled. If there is little response after 12 months, reassessment may recommend surgery as an option in failed medical management.

The majority (50-80%) of patients will require some form of surgery in their lifetime, to treat acute septic complications, perianal disease and chronic manifestations such as strictures, or following failure of medical therapy.

Common operations include resection for bowel obstruction (with or without ileostomy), drainage of abscesses and stricturoplasty (open or endoscopic). Colonic surgery includes partial or total colectomy and proctectomy.

Early elective surgery should be considered in patients with disease limited to the terminal ileum, in children with limited disease when growth is affected, and in those not responding to medical treatment.

Surgery is not curative for CD, so patients may still require medical treatment to maintain remission.

New developments
Pharmacotherapy forms the mainstay of new treatment research in CD. Whilst the role of monoclonal antibodies is still being established, recent interest has focused on `biosimilar' drugs, those biologically similar to infliximab, which have recently been authorised for use in CD and are currently undergoing trials.

The early promising results of the Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) trial, investigating the role of stem cell transplantation in treatment-resistant Crohn's, were not maintained and currently HSCT is not recommended for patients with refractory Crohn's.11  

A new class of biological drugs called anti-integrin antibodies have been introduced (vedolizumab) which target the problem of vascular permeability within the inflamed intestinal endothelium by inhibiting leukocyte migration, and may offer hope to patients in whom infliximab has failed.12

Section 4: Prognosis

Crohn’s disease is a chronic relapsing condition.  In the first 12 months after diagnosis, relapse occurs in almost half of patients, and 10% have a chronic relapsing course.

Many patients will require surgery for complications of CD, with the cumulative probability increasing over time, so that at 15 years the cumulative probability of having one surgical procedure is 34%, two or more 36% and none 30%.13

Patients whose acute CD is discovered during laparotomy or investigations for suspected appendicitis have a better prognosis. Most cases are treated conservatively and up to two-thirds have no further regional enteritis.13

There is conflicting evidence regarding overall mortality, which seems to be subject to geographical variation. 14,15

There appears to be an increased incidence of lung malignancy, COPD and GI malignancy.16

With appropriate medical and surgical management, patients with CD can expect a good prognosis and reasonable quality of life. It is thought that with improved medical management, there is a trend towards reduced risk of developing colorectal cancer, although regular surveillance should still be offered to all patients with Crohn's colitis.17

Section 5: Case study

A 23-year-old male presented to A&E with a two-day history of right iliac fossa pain associated with vomiting and fever.

The patient's past medical history included incision and drainage of a perianal abscess when he was 18 years old.

He had a two-month history of weight loss and fatigue, which he put down to recent stress at work.

It was thought that the patient had acute appendicitis. He was treated with IV antibiotics and laparoscopic appendectomy was performed.

Right iliac fossa pain
Although the appendix looked macroscopically normal, the patient's symptoms settled and he was discharged after three days on oral antibiotics.

Subsequent histology demonstrated a normal appendix and no follow-up was arranged.

Five weeks later he presented to the hospital with a similar right iliac fossa pain and fever, with an elevated WCC and CRP.

A CT scan was performed, demonstrating thick-walled terminal ileum with adjacent fat stranding, suggestive of CD.

Subsequent colonoscopy with biopsies of the terminal ileum revealed lymphoid aggregates, granulomas and skip lesions, and a diagnosis of CD was made.

The patient was referred to the gastroenterologists and started on corticosteroids, with a prompt improvement in his symptoms.

Over the next year, he had four episodes of abdominal pain and bloating, which culminated in bowel obstruction requiring laparotomy and small bowel resection of a strictured segment.

Following his recovery from surgery, he continued on maintenance methotrexate and his symptoms remained manageable with regular visits to the outpatients department.

Section 6: Evidence base

Clinical trials

  • A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. S.R. Targan, S.B. Hanauer, S.J. van Deventer, et al. N Engl J Med 1997; 337: 1029-35 The first randomised controlled trial of biological agents in Crohn's disease. It reported a moderate efficacy in inducing remission (65% vs 17% at 4 weeks, and 41% vs 12% at 12 weeks following a single dose infliximab vs placebo)
  • The ACCENT I and ACCENT II trials - These sponsored trials showed limited maintenance of remission with infliximab (35% v 15% placebo at one year). ACCENT II, looking at perianal and enterocutaneous fistulas, found 30% of patients treated maintained response at a year, compared with 19% in the placebo group.
    • Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002; 359: 1541-9.
    • Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004; 350: 876-85.
  • Colorectal Surgery: A Companion to Specialist Surgical Practice, 4th Edition.  Chapter 10 - Crohn’s Disease.  M W Thompson-Fawcett & N J McC. Mortensen. Ed Robin KS Philips.  4th Edition 2009. Saunders Elsevier. A Comprehensive overview on the medical and surgical aspects of Crohn’s disease


Patient information

  • Crohn's and Colitis. Information about IBD. - Patient information includes support for young people, treatment, information for families, employment, and fertility and pregnancy.

Contributed by Dr Abdullah Rana, surgical trainee, and Mr Joseph Dawson, consultant surgeon, University of Adelaide & The Queen Elizabeth Hospital, Adelaide, South Australia.

Take a test on this article and claim your certificate on MIMS Learning

This is an updated version of an article that was first published in September 2013.


  1. NICE. Crohn's disease: management in adults, children and young people. CG152. October 2012.
  2. Steed H, Walsh S, Reynolds N. Scot Med J 2010; 55(3): 22-5.
  4. Parkes M. Digest Dis 2012; 30 Suppl 1: 78-81.
  5. Dyson JK, Rutter MD. World J Gastroenterol 2012; 18(29): 3839-48.
  6. Silverberg MS, Satsangi J, Ahmad T et al. Can J Gastroenterol 2005; 19(suppl A)5-36.36.
  7. Walker LJ, Aldhous MC, Drummond HE et al. Clin Exp Immunol 2004; 135(3): 490-6.
  8. Albert JG, Martiny F, Krummenerl A et al. Gut 2005; 54(12): 1721-7.
  9. NICE. TA187.
  10. Thompson-Fawcett MW, Mortensen NJM. Crohn's Disease. In: Phillips R (ed). Colorectal Surgery: A Companion to Specialist Surgical Practice (fourth edition). London, WB Saunders, 2008.
  11. Hawkey CJ et al. JAMA 2015; 314(23): 2524-2534
  12. Sandborn WJ, Feagan BG, Rutgeerts P, et al. N Eng J Med. 2013;369:711-21
  13. Ghazi LJ.
  14. Jess T, Frisch M, Simonsen J. Clin Gastroenterol Hepatol. Jan 2013;11(1):43-8
  15. Jess T, Loftus EV Jr, Harmsen WS, Zinsmeister AR, et al. Gut. 2006;55(9):1248-54
  16. Munkholm P, Langholz E, Davidsen M et al. Gastroenterol 1993; 105(6): 1716-23.
  17. NICE Colonoscopic surveillance for prevention of colorectal cancer in people with ulcerative colitis, Crohn’s disease or adenomas. CG118 March 2011
Suggested further CPD activity
  • Audit patients on immunosupressant drugs with CD and ensure appropriate monitoring is being undertaken.
  • Organise six-monthly reviews of patients with CD to assess their use of steroids and consider stepping up treatment.
  • Review patients with CD, looking for dermatological, skeletal and ophthalmic manifestation of the condition, and organise the management of these associated problems.

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