Crohn’s Disease

Crohn’s disease (CD) is a type of chronic inflammatory bowel disease (IBD), the other main form being Ulcerative Colitis (UC).

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

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

Pathophysiology

CD can affect any part of the gastrointestinal tract (from mouth to anus) but most commonly targets the distal ileum or proximal colon, however much of its aetiology still 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. The episodes often come in acute attacks before entering remission.

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

Fig 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 (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
    • Can present as skin tags, perianal abscesses, fistulae, or bowel stenosis

Examination features include abdominal tenderness and distention, 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 (reduced absorption of bile salts which leads to increased free oxalate)
Fig 2 - Extra-intestinal manifestation of Crohn's disease: (A) Erythema nodosum (B) Pyoderma gangrenosum

Fig 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 raised CRP and WCC. Liver function tests may become deranged in patients on treatment. In the acute situation, an abdominal x-ray(AXR) may be useful to exclude any potential toxic megacolon or bowel obstruction that may have occurred.

NICE guidelines recommend that faecal calprotectin testing is carried out in patents with recent onset lower gastrointestinal symptoms; it is raised in inflammatory bowel disease, but unchanged in irritable bowel syndrome. A stool sample sent for MC&S for any potential infective cause can be considered,

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

Fig 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. A characteristic macroscopic finding is cobblestoning of the bowel (fissures and ulcers separate islands of healthy mucosa), with a non-caseating granulomatous inflammation.
    • This should be avoided during an active flare, due to increased risk of potential perforation, and a flexible sigmoidoscopy may be warranted instead in such cases
  • Barium swallow – less commonly performed, yet can show strictures, ‘rose thorn’ ulcers, and the ‘string sign of Kantor’.
  • CT scan – usually warranted in severe Crohn’s disease, which may demonstrate bowel obstruction, perforation, collection formation, or fistulae.

For perianal disease, a pelvic MRI is first line as it is both accurate and non-invasive. Examination under anaesthesia with proctosigmoidoscopy may also be considered to examine for concomitant rectosigmoid inflammation.


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 (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).

Further Management

Patients should be referred to IBD-nurse specialists and patient support groupsEnteral 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

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.

The most common procedure is ileocaecal resection, removal of terminal ileum and caecum with primary anastamosis between ileum and ascending colon. Various other surgical procedures may be used, however in all cases a bowel-sparing approach must be taken to prevent short gut syndrome in later years.


Complications

Gastrointestinal

  • Stricture formation
    • Inflammation of the bowel can result in stricture formation, resulting in bowel obstruction and perforation
  • Fistula, including enterovesical*, enterocutaneous, or rectovaginal fistula
    • Fistulas can be removed by fistulotomy (i.e. opening the tract up) or Seton technique (where a cord is tied around the fistula which keeps the fistula open and over time the fistula drains and eventually heals over)
  • Perianal complications
    • Common in patients with Crohn’s Disease, includes the formation of perianal abscesses or fistulae
  • GI malignancy
    • Patient’s with Crohn’s disease have about a 3% risk of developing colorectal cancer over 10 years.
    • Small bowel cancer is about 30x more common in those with Crohn’s disease than the general population.

* Enterovesical fistula will often present with recurrent UTIs and pneumaturia, requiring a MRI scan for definitive diagnosis

Extraintestinal

  • Malabsorption
    • Including growth delay in children
  • Osteoporosis
    • 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, yet mostly affects the terminal ileum
  • Definitive diagnosis is made from colonoscopy with biopsy, yet this should not be done during acute attacks
  • Medical management of acute flares involves sequential escalation of treatment, from corticosteroids and immunosuppressors to biological therapies
  • Surgical input should be sort urgently in cases refractory to medical management, patients who have developed toxic megacolon, or suspected bowel perforation
  • Complications of the disease can be both intestinal and extra-intestinal manifestations

Quiz

Question 1 / 4
Which of the following is not associated with Crohn's dosease

Quiz

Question 2 / 4
Which of the following investigations should not be performed during an acute flare of CD?

Quiz

Question 3 / 4
A 44yr old patient with known CD is admitted with an acute flare of the disease. A CT scan shows severe inflammation of the terminal ileum, with no further complications evident. Clinically, she does not improve medical management, including Infliximab therapy, and is deteriorating. What is the next suitable management step

Quiz

Question 4 / 4
Which of the following complications are CD patients most at risk of developing?

Results

Further Reading

Management of active Crohn disease
Cheifetz AS, JAMA

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