Part of the TeachMe Series

Crohn’s Disease

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Original Author(s): Sittiga Hassan
Last updated: October 27, 2019
Revisions: 60

Original Author(s): Sittiga Hassan
Last updated: October 27, 2019
Revisions: 60

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Introduction

Crohn’s disease (CD) is one of the main types of inflammatory bowel disease (IBD), the other being Ulcerative Colitis (UC).

The prevalence of the condition is about 150 per 100,000 people in the UK ( being slightly less common than UC) and has a bimodal peak age of presentation of between 15-30 years and then again at 60-80 years.

The disease typically follows a remitting and relapsing course. Severe exacerbations may be life- threatening, causing severe systemic upset, bowel perforation or obstruction.

Pathophysiology

Crohn’s disease can affect any part of the gastrointestinal tract (from mouth to anus), although commonly targets the distal ileum or proximal colon, however much of its aetiology remains unknown. Much like UC, Crohn’s disease appears to have a familial link, however unlike UC smoking increases your risk of developing the condition.

It is characterised by transmural inflammation (affecting all layers of the bowel) in the affected region of bowel, producing deep ulcers and fissures (a ‘cobblestone’ appearance’). The inflammation is not continuous, forming skip lesions throughout the bowel.

The microscopic appearance of Crohn’s disease is non-caseating granulomatous inflammation.

Ulcerative Colitis Crohn’s Disease
Site Involvement Large bowel Entire GI tract
Inflammation Mucosa only Transmural
Microscopic Changes Crypt abscess formation
Reduced goblet cells
Non-granulomatous
Granulomatous (non-caseating)
Macroscopic Changes Continuous inflammation (proximal from rectum)
Pseudopolyps and ulcers may form
Discontinuous inflammation (‘skip lesions’)
Fissures and deep ulcers (‘cobblestone appearance’)
Fistula formation

Table 1 – Characteristic Features of Inflammatory Bowel Disease

Due to the transmural nature of the inflammation, fistula can form from affected bowel to adjacent structures, resulting in perianal fistula (54%), entero-enteric fistula (24%), recto-vaginal (9%), entero-cutaneous fistula, or entero-vesicalar fistula.

Risk Factors

The aetiology of Crohn’s disease is unknown, yet both environmental factors and genetic factors are thought to play a role. The main risk factors for CD include:

  • Family history
    • 20% have first degree relative affected.
  • Smoking
    • Increases the risk of developing Crohn’s disease and risk of relapse.
  • White European descent (particularly Ashkenzi Jews)
  • Appendicectomy
    • Increases the risk of developing CD directly after the surgery

Clinical Features

Crohn’s disease typically presents with episodic abdominal pain and diarrhoea. The abdominal pain may be colicky in nature and will vary in site depending on the region of bowel involved. Diarrhoea is often chronic and may contain blood or mucus.

Fig 1 - Aphthous oral ulcer in active Crohn's disease

Figure 1 – Aphthous oral ulcer in active Crohn’s disease

Systemic symptoms include malaise, anorexia and low-grade fever. It may also result in malabsorption and malnourishment if severe, albeit typically a late presenting feature (in children, this may initially present as a failure to grow or thrive).

As the disease affects the entire GI tract, both oral and perianal involvement are common:

  • Oral aphthous ulcers (can be painful and recurring)
  • Perianal disease (as skin tags, perianal abscesses, fistulae, or bowel stenosis)

Examination features include abdominal tenderness, mouth or perianal lesions, and signs of malabsorption or dehydration. Patients should also be examined for extra-intestinal features.

Extra-Intestinal Features

Crohn’s disease, much like Ulcerative Colitis, is associated with several extra-intestinal manifestations of the disease:

  • Musculoskeletal
    • Enteropathic arthritis (typically affecting sacroiliac and other large joints) or nail clubbing
    • Metabolic bone disease (secondary to malabsorption)
  • Skin
    • Erythema nodosum  – tender red/purple subcutaneous nodules, typically found on the patient’s shins (Fig. 2A)
    • Pyoderma gangrenosum – erythematous papules/pustules that develop into deep ulcers (Fig. 2B) and can occur anywhere (yet typically affect the shins)
  • Eyes – Episcleritis, anterior uvetitis, or iritis
  • Hepatobiliary – Primary sclerosing cholangitis (more associated with UC), cholangiocarcinoma (due to association with primary sclerosing cholangitis), and gallstones
  • Renal: Renal stones
Fig 2 - Extra-intestinal manifestation of Crohn's disease: (A) Erythema nodosum (B) Pyoderma gangrenosum

Figure 2 – Extra-intestinal manifestation of Crohn’s disease: (A) Erythema nodosum (B) Pyoderma gangrenosum

Investigations

Routine bloods are required to examine for anaemia, low albumin (secondary to malabsorption), and evidence of inflammation (raised CRP and WCC).  In the acute situation, an abdominal radiograph (AXR) or CT imaging may be useful to exclude any potential toxic megacolon or bowel obstruction that may have occurred.

A faecal calprotectin test should be performed in all patents with recent onset lower gastrointestinal symptoms, with a good sensitivity for inflammatory bowel disease. A stool sample for any potential infective cause can also be considered.

Fig 3 - Endoscopic image of Crohn's colitis showing deep ulceration

Figure 3 – Endoscopic image of Crohn’s colitis showing deep ulceration

There are three main types of imaging that can be utilised in the diagnosis of Crohn’s disease:

  • Colonoscopy with biopsy – the gold standard diagnostic investigation; a characteristic macroscopic finding is cobblestoning of the bowel (fissures and ulcers separate islands of healthy mucosa), with non-caseating granulomatous inflammation on histology
  • CT scan – usually warranted in severe Crohn’s disease, which may demonstrate bowel obstruction, perforation, collection formation, or fistulae
  • MRI scan – for the same indications as CT scanning but in the non-acute (elective) setting, particularly useful for looking for enteric fistulae and for peri-anal disease (as well as reducing radiation dosing)

Examination under anaesthesia with proctosigmoidoscopy may also be considered to examine and treat fistulating peri-anal disease.

Management

Patients with suspected IBD should be referred to a gastroenterologist for confirmation of the diagnosis and initiation of treatment; those with acute severe disease should be admitted on an emergency basis.

Anti-motility drugs, such as loperamide, should be avoided in acute attacks, as these can precipitate toxic megacolon.

Inducing Remission

Any acute attacks will also warrant aggressive fluid resuscitation, nutritional support, and prophylactic heparin and anti-embolic stockings (due to the prothrombotic state of IBD flares).

The medical management to induce remission in Crohn’s Disease requires use of corticosteroid therapy and immunosuppresive agents, such as mesalazine or azathioprine. Biological agents, such as infliximab, can be trialled as rescue therapy if then needed.

Maintaining Remission

Azathioprine or mercaptopurine are recommended as a monotherapy to maintain remission. Methotrexate can be considered in those who have used it to induce their remission or cannot tolerate other maintenance therapies.

In recent years with the development of biological agents, patients can be started on infliximab, adalumimab, or rituximab if there has been a failure of treatment with other agents. These are often also used as rescue therapy during acute flares in those who have not responded to first line remission agents.

Smoking cessation is advised. Due to increased risk of colorectal malignancy, colonoscopic surveillance is offered to people who have had the disease for >10 years with >1 segment of bowel affected (follow-up time frame depends on risk stratification of disease following initial endoscopy).

Patients should be referred to IBD-nurse specialists and patient support groups. Enteral nutritional support should be considered in young patients with growth concerns, with close support from nutritional teams. Antibiotics are only offered to those with obvious concurrent infection or perianal disease (typically ciprofloxacin or metronidazole).

Surgical Management

Around 70-80% of Crohn’s patients require surgery at some point in their lifetime.

Surgical intervention is indicated in those with failed medical management, severe complications (such as strictures or fistulas), or growth impairment in younger patients.

Operations* that are commonly required in patients with Crohn’s disease include:

  • Ileocaecal resection (removal of terminal ileum and caecum with primary anastomosis)
  • Surgery for peri-anal disease (e.g. abscess drainage, seton insertion, or laying open of fistulae
  • Stricturoplasty (division of a stricture that is causing bowel obstruction)
  • Small bowel or large bowel resections

CD patients are typically high risk patients to operate on, therefore pre-operative optimisation (including treating any acute attack and managing nutrition) should be attempted where possible. In all proposed operations, a bowel-sparing approach must be taken to prevent short gut syndrome in later years

Complications

Gastrointestinal

  • Fistula, including enterovesical, enterocutaneous, or rectovaginal fistula
  • Stricture formation
    • Inflammation of the bowel can result in stricture formation, resulting in bowel obstruction
  • Recurrent perianal abscesses / fistulae
    • These are common and often difficult to treat, requiring multiple operations / examinations under anaesthesia
  • GI malignancy
    • Patient’s with Crohn’s disease have about a 3% risk of developing colorectal cancer over 10 years and small bowel cancer is about 30x more common in those with Crohn’s disease

Extraintestinal

  • Malabsorption
    • Including growth delay in children
  • Osteoporosis, particularly common if there is obstruction or fistula formation
    • Secondary to malabsorption or long-term steroid use
  • Increased risk of gallstones
    • Due to reduced reabsorption of bile salts at inflamed terminal ileum
  • Increased risk of renal stones
    • Due to malabsorption of fats in the small bowel which causes calcium to remain in the lumen; oxalate is then absorbed freely (as normally bound to calcium and excreted in stool), resulting in hyperoxaluria and formation of oxalate stones in the renal tract

Key Points

  • Crohn’s disease can affect any part of the gastrointestinal tract; the most common site is the terminal ileum
  • Definitive diagnosis is made from colonoscopy and biopsy
  • Medical management of acute flares involves sequential escalation of treatment, from corticosteroids and immunosuppressors to biological therapies
  • Surgical input should be sought urgently in cases refractory to medical management, patients who have developed toxic megacolon, or suspected bowel perforation
  • These patients are often very unwell, therefore close attention to detail, in particular to their nutritional status, is essential