Crohn's disease


Definition & classification

Crohn's disease is a chronic inflammatory disorder, which can affect any part of the gastrointestinal tract from mouth to anus.

Inflammatory bowel disease (IBD) is an umbrella term for two chronic inflammatory disorders of the gastrointestinal system: ulcerative colitis (UC) and Crohn’s disease (CD).

The overall incidence of CD is estimated to be 6 per 100,000 population, although this varies considerably between countries. It has bimodal incidence with peaks between the ages of 15-30 and 60-80 years old. 

Classification of IBD


CD is thought to result from an abnormal immunological response to one or more aetiological factors within a genetically susceptible individual. 

Genetic, immunological and environmental factors have all been implicated in the development of CD. 

Aetiology of Crohns


CD is a polygenic disease (that is, multiple genetic loci increase the likelihood of developing CD, but do not directly cause it). There is an association between single nucleotide polymorphisms (SNP) in the NOD2 (CARD15) gene and CD. Additional genetic loci have also been identified that increase the risk of CD. With these in mind, it is important to be thorough when taking a history as patients may have a positive family history.

Immune system

Some research suggests that there may be an abnormal immunological response to normal intestinal microflora. Typically, a Th1 helper cell predominant response is seen leading to increased levels of pro-inflammatory cytokines (e.g. TNF-alpha).


Smoking increases the risk of CD, whereas rather peculiarly, it is protective in UC. Smoking also has implications on disease severity and relapses.

There are also numerous other environmental factors associated with CD including western diets, antibiotic and contraceptive use.


CD can affect any part of the GI tract from the mouth to the anus. 

Approximately 80% of patients have evidence of small bowel disease, which occurs most commonly in the distal ileum (terminal ileitis).  50% have evidence of small bowel and colonic disease. 33% have small bowel disease only. Around 20% of patients have colonic disease only. This can make it difficult to distinguish between CD and UC.

33% of patients suffer from perianal Crohn's disease. This includes a variety of conditions that affect the perianal area (e.g. skin tags, fissures, fistulae, abscesses, or anal canal stenosis).

A number of pathophysiological changes occur in Crohn’s disease due to chronic inflammatory processes. These changes can be considered as macroscopic (seen during endoscopy) or microscopic changes (seen on histology).

Pathophysiology of Crohn's


A number of signs may be seen at the time of endoscopy. A cobblestone appearance is classical, this is caused by small superficial ulcers which become deep and serpiginous (wavy margin). These may be transverse to longitudinal giving the mucosa its classical cobblestone appearance.

Bowel wall thickening, lumen narrowing, deep ulcers, fistulae and fissures may also be seen.


Inflammatory infiltration is noted on histology. This is characterised by lymphoid hyperplasia and non-caseating granulomas.

Skip lesions and transmural ulceration are also seen.

Clinical features

The clinical presentation of CD is variable, depending on both extent of disease and location of pathology. 

Characteristic features of CD include diarrhoea, abdominal pain, weight loss, fever and fatigue. Patients with CD are at risk of a number of intestinal complication due to wall thickening, lumen narrowing and ulceration.


  • Nausea & vomiting
  • Fatigue
  • Low-grade fever
  • Weight loss
  • Abdominal pain
  • Diarrhoea (+/- blood)
  • Rectal bleeding
  • Perianal disease


  • Pyrexia
  • Dehydration
  • Angular stomatitis
  • Aphthous ulcers
  • Pallor
  • Tachycardia 
  • Hypotension
  • Abdominal pain, mass and distension

Crohns clinical features

Perianal disease

Perianal Crohn's disease refers to a collection of perianal pathology commonly associated with the condition.

Perianal Crohn's disease can affect up to one-third of patients. Skin tags, fissures, fistulae, abscesses and anal canal stenosis may all be seen.

Perianal symptoms are typically non-specific and inspection of the perineum is critical. Symptoms include rectal bleeding, pruritus and pain

Extra-intestinal manifestations

Extra-intestinal manifestations (EIM) refer to the collection of clinical features that occur outside the gastrointestinal tract within CD.


Musculoskeletal disease is the most common extra-intestinal manifestation. Two forms of arthritis are seen, type 1 and type 2.

  • Type 1 is a pauciarticular peripheral arthritis related to intestinal disease activity.
  • Type 2 is a polyarticular peripheral arthritis independent of intestinal disease activity.

Large joints are affected in up to 20% and ankylosing spondylitis and sacroiliitis may occur.


The skin is affected in around 10 - 20% of cases. Two of the lesions seen are erythema nodosum and pyoderma gangrenosum.

Erythema nodosum, a panniculitis, is characterised by reddened, raised, tender nodules. 

Pyoderma gangrenosum presents with ulcerating nodules characterised by black (gangrenosum) edges and central pus (pyoderma).

Eyes & mouth

The eyes are involved in around 5% of cases. Episcleritis is the most common manifestation. Uveitis and conjunctivitis also occur. 

Aphthous ulcers are often seen in Crohn's patients, they may precede intestinal disease.


The hepatobiliary system may be affected in a number of ways. Primary sclerosing cholangitis may occur though it is more common in UC.

Fatty liver disease and gallstones are seen with increased frequency.


  • Renal calculi
  • Osteoporosis
  • B12 deficiency
  • Pulmonary disease
  • Venous thrombosis
  • Anaemia

Investigations and Diagnosis

The diagnosis of CD is based on macroscopic assessment (e.g. endoscopy) and histological evidence (e.g. biopsy) of inflammation typical of CD. 


  • Observations
  • ECG
  • Urinalysis
  • Stool microscopy, culture & sensitivities + ova, cysts & parasites + C. diff toxin (CDT)
  • Faecal calprotectin:
    • Sensitive marker of intestinal inflammation. Released following degranulation of neutrophils.


  • Full blood count (FBC)
  • Liver function tests (LFTs)
  • Urea & electrolytes (U&Es)
  • CRP
  • Magnesium
  • Haematinics
  • Auto-antibodies (ASCA (antibody to Saccharomyces cerevisiae) more common in CD than UC)
  • Bone profile
  • Clotting


Abdominal X-ray reveals bowel dilatation and perforation in the acute setting. Abdominal USS can be used to assess for wall thickening, free-fluid or abscess formation.

Computed tomography demonstrates bowel wall thickening, bowel obstruction, abscesses, or fistulae. It is good at the assessment of extra-mural complications. Magnetic resonance imaging is important in the evaluation of small bowel and perianal disease.

Barium imaging helps to assess the extent of small bowel disease, particularly strictures. 


Ileocolonoscopy is used to assess the colon & terminal ileum. It provides an opportunity for tissue biopsy with a positive predictive value of 100%.

Upper GI endoscopy is indicated in patients with gastroduodenal disease. A biopsy is needed to differentiate Crohn’s from other pathology (e.g. PUD).

Examination under anaesthetic (EUA) is the gold-standard for assessment of certain types of perianal disease.


The general principle in the management of CD is to induce and then maintain remission

Induce remission

The first presentation or a single acute inflammatory exacerbation within 12 month period is managed with oral corticosteroids. If corticosteroids are contraindicated, 5-ASA compounds and budesonide may have a role.

Enteral nutrition can be used as an alternative to induce remission in children where there is a concern about growth.

Azathioprine or mercaptopurine can be used in addition to standard corticosteroid therapy. They are typically reserved for patients presenting with 2+ inflammatory exacerbations within a 12 month period. Methotrexate is an alternative immunosuppressive agent that can be used.

Anti-TNF-alpha monoclonal antibodies (e.g.Infliximab and adalimumab) are recommended for adults with severe active Crohn's disease that has not responded to initial therapy. Monoclonal antibodies should be given with the intention of treating for a minimum of 12 months or until medical therapy has failed. 


Azathioprine or mercaptopurine monotherapy is utilised once remission is achieved.

With both of these drugs, pre-administration assessment of thiopurine methyltransferase (TPMT) needs to be checked. TPMT is one of the enzymes involved in the metabolism of azathioprine and mercaptopurine (azathioprine is a pro-drug of mercaptopurine). Patients with low levels of this enzyme are at risk of life-threatening bone marrow suppression

Methotrexate can be used as an alternative monotherapy


Surgery is common in Crohn’s disease, utilised in 50-80% of cases. It is indicated in acute flares refractory to medical management or patients at risk of (or who have suffered) perforation.

It may be utilised before or early in puberty in children and young people who have poor growth despite medical therapy.

Surgery is also indicated in the management of a number of complications (e.g. strictures)

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