Crohn’s Disease

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 rarely death.

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, CD 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 (Table 1).

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

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

Table 1 – Characteristic Features of Inflammatory Bowel Disease

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 strong family history (20% have first degree relative affected) and smoking (increases both the risk of developing Crohn’s disease and the risk of relapse), and

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.

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, Fig.1)
• Perianal disease, including with perianal abscess

By TheBlunderbuss [CC-BY-SA-3.0], via Wikimedia Commons

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

Extra-Intestinal Features

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

• Musculoskeletal, such as Enteropathic arthritis (typically affecting sacroiliac and other large joints), nail clubbing, or with metabolic bone disease (secondary to malabsorption)

• Skin, either as erythema nodosum (tender red/purple subcutaneous nodules, typically on the shins (Fig. 2A)) or pyoderma gangrenosum (erythematous papules/pustules that develop into deep ulcers (Fig. 2B))
• Eyes – Episcleritis, anterior uvetitis, or iritis

• Hepatobiliary – Primary sclerosing cholangitis (more associated with UC), cholangiocarcinoma (due to association with primary sclerosing cholangitis), or gallstones

• Renal – Renal stones (see Complications section)

Adapted from work by James Heilman and Monopol [CC BY-SA 3.0], via Wikimedia Commons

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 systemic illness), and evidence of inflammation (raised CRP and WCC).

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 should also be sent.

However, colonoscopy is the gold standard investigation, whereby biopsies can be taken to confirm the diagnosis; in cases without any colonic or terminal ileal disease (i.e. more proximal disease) and biopsies are not able to be obtained, presumed diagnosis can sometimes be made on clinical features and imaging alone.

Imaging

A CT scan abdomen pelvis usually warranted in severe Crohn’s disease, as it can demonstrate bowel obstruction (from stricturing), bowel perforation, or intra-abdominal collections; this is especially useful in the acute phase.

MRI imaging can also be used to assess disease severity, both with small bowel involvement and presence of any enteric fistulae (via a MRI small bowel) and for peri-anal disease (via a MRI pelvis). Subsequent Examination Under Anaesthesia (EUA) with proctosigmoidoscopy may also be considered to examine and treat perianal fistulae present.

Samir, CC BY-SA 3.0 , via Wikimedia Commons

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

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 as first line. Subsequent treatments, including immunosuppresive agents, such as mesalazine or azathioprine, or biological agents, such as infliximab or adalimumab, can be trialled as rescue therapy if then needed.

Maintaining Remission

Azathioprine is recommended as a monotherapy to maintain remission as first line. Smoking cessation is also advised where applicable.

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.

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 or severe complications (such as strictures or perforation). In all proposed operations, a bowel-sparing approach must be taken to prevent short gut syndrome in later years.

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

• Ileocaecal resection (removal of terminal ileum and caecum with primary anastomosis)
• Small bowel resection or large bowel resection
• 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)

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 those with an active severe flare, a primary bowel anastomosis should not be performed (or at least not without a defunctioning stoma), due to the risk of breakdown at the anastomosis

Complications

Gastrointestinal

• Fistula, including enterovesical, enterocutaneous, or rectovaginal fistula
• Stricture formation
• Recurrent perianal fistulae – These are common and often difficult to treat, requiring multiple operations to manage
• 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, secondary to malabsorption or long-term steroid use
• Increased risk of gallstones, due to reduced reabsorption of bile salts at the 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