Crohn’s Disease | Inflammatory Bowel Disease

Introduction
Crohn’s disease is a chronic, relapsing-remitting, non-infectious inflammatory disease of the gastrointestinal tract.
It is a type of inflammatory bowel disease (IBD), an umbrella term which also includes ulcerative colitis (UC).1
Patients typically present between 20-40 years old, and Crohn’s disease has an incidence of around 10-20/10000/year.2
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Aetiology
The aetiology of Crohn’s disease is still unclear. However, it is thought to be an inappropriate immune response to an environmental trigger in a genetically susceptible individual.
Around 15% of affected people have a first-degree relative with the disorder. However, it is important to remember that it is most likely caused by a combination of genetics, environment and lifestyle factors.3
Crohn’s disease can affect a patient anywhere from the mouth to the anus:1

80% of patients have evidence of small bowel disease, most commonly occurring in the distal ileum (terminal ileitis)
25% of patients suffer from perianal disease

Pathophysiology
Chronic inflammation leads to pathophysiological changes, which can be seen microscopically (on histology) and macroscopically (on endoscopy).
Microscopic features
Histological features include inflammatory infiltration, characterised by lymphoid hyperplasia and non-caseating granulomas. Transmural inflammation is also seen.
Macroscopic features
Initially, small superficial ulcers (aphthous ulcers) form due to inflammation. Over time, they become deep and serpiginous, giving the mucosa its classical cobblestone appearance, which can be seen on endoscopy. There may be bowel wall thickening, fistulae and fissures.

Risk factors
Risk factors for Crohn’s disease include:4

Family history
Cigarette smoking
Previous infectious gastroenteritis
NSAID usage
A diet high in refined sugar and low in fibre

Clinical features
History
Typical symptoms of Crohn’s disease include:1,2

Abdominal pain: most commonly in the right lower quadrant (terminal ileum) and peri-umbilical regions
Diarrhoea: bloody or non-bloody, may be accompanied by mucus, and nocturnal diarrhoea may occur
Perianal pain/itching: if perianal disease
Oral ulceration (aphthous ulcers) (Figure 1)
Nausea and vomiting
Fever
Fatigue
Weight loss

Other symptoms may relate to the extra-intestinal manifestations of Crohn’s disease.5

Extra-intestinal manifestations of Crohn’s disease
Extraintestinal manifestations in Crohn’s disease include:

Musculoskeletal: enteropathic arthritis
Eyes: episcleritis, uveitis (Figure 2) and conjunctivitis
Skin: erythema nodosum (Figure 3) and pyoderma gangrenosum
Hepatobiliary: primary sclerosing cholangitis, fatty liver disease and gallstones
Renal: nephrolithiasis
Haematological: anaemia, B12 deficiency and thromboembolism

Clinical examination
Typical clinical findings on examination include:1

Abdominal tenderness or mass
Perianal tenderness or pain, anal or perianal skin tags, fissure, fistula or abscess
Features of anaemia (e.g. pallor, fatigue and conjunctival pallor)
Joint pain
Clubbing
Oral lesions: aphthous ulcers

 

Differential diagnoses
Differential diagnoses to consider include:4

Crohn’s disease vs. ulcerative colitis
Table 1. A summary of the key differences between Crohn’s disease and ulcerative colitis.

 
Crohn’s disease
Ulcerative colitis

Location
Whole gastrointestinal tract
Colon (mainly rectum)

Type of lesion
Transmural inflammation
Superficial ulcers

Characteristic pattern
Skip lesions
Continuous lesions

Microscopic findings
Non-caseating granulomas
Crypt abscesses

Macroscopic findings
Cobblestone appearance
Friable mucosa

Complications

Strictures
Bowel obstruction
Fistulas
Perianal abscesses

Gastrointestinal bleeding
Toxic megacolon
Peritonitis
Adenocarcinoma

Treatment options

Immunosuppressants (e.g. corticosteroids)
Aminosalicylates (e.g. mesalazine)
Antibiotics (e.g. ciprofloxacin and metronidazole)
Biologics (e.g. infliximab)
Immunomodulators (e.g. azathioprine)
Surgery (not curative)

Immunosuppressants (e.g. corticosteroids)
Aminosalicylates (e.g. mesalazine)
Biologics (e.g. infliximab)
Surgery (curative)

Investigations
A diagnosis of Crohn’s disease is made based on features of the clinical history and endoscopic findings. However, it is important to exclude any other causes of colitis and diarrhoea first.2
Laboratory investigations
Relevant laboratory investigations include:1

Stool testing
Faecal calprotectin is a sensitive marker of gastrointestinal inflammation and can help distinguish inflammatory bowel disease (IBD) from non-inflammatory gastrointestinal conditions (e.g. irritable bowel syndrome). It is raised in Crohn’s disease and can be used as a marker of disease activity.
Sending a stool microscopy, culture and sensitivity (MC&S) is important to exclude infection (e.g. Clostridium difficile).
Gastrointestinal endoscopy
Colonoscopy and biopsy is the preferred way to diagnose Crohn’s disease. It is used to assess the colon and the terminal ileum.
An upper gastrointestinal endoscopy is used to assess for gastroduodenal disease.

Endoscopic features of Crohn’s disease
Macroscopic features of Crohn’s disease on endoscopy include:

Cobblestone appearance: small superficial ulcers
Skip lesions
Oedema
Hyperaemia
Aphthous ulcers
Rose thorn ulcers: deep penetrating linear ulcers seen around a stenosed terminal ileum.

Microscopic histology features include:

Transmural involvement with non-caseating granulomas
Lymphoid hyperplasia

Imaging
Imaging is used in acute presentations (e.g. to identify complications) and to assess the progression of Crohn’s disease.
Relevant imaging investigations include:

Abdominal X-ray: may identify bowel dilatation and perforation in acute settings
Abdominal ultrasound: can be used to assess bowel thickening, free-fluid or abscess formation
CT abdomen: usually used in the acute setting and to assess for complications (especially extra-mural complications)
MRI small bowel/pelvis: can be used for ‘disease mapping’; assesses the extent of inflammation in the small bowel or fistulae formation

Management
Management of Crohn’s disease aims to induce remission and maintain remission.9
Management plans are usually complex and require the patient to be under the care of a gastroenterologist, with the support of specialist nurses. Treatment plans are dependent on disease severity, co-morbidities and the presence of any complications.
Patients should be advised to stop smoking, which can reduce disease activity and the risk of complications. 
Inducing remission
Initial monotherapy for inducing remission may include:

Corticosteroids (e.g. prednisolone, methylprednisolone or intravenous hydrocortisone): used to induce remission in patients with first presentation or a single inflammatory exacerbation in a 12-month period.
Budesonide: if conventional steroid use is unsuitable, however, it is less effective.
Aminosalicylates (e.g. sulfasalazine or mesalazine): these cause fewer side effects than corticosteroids and budesonide but are not as effective; they are unsuitable for severe presentations.

Add-on treatment
The following can be added to a corticosteroid after two or more exacerbations in a 12-month period or if the corticosteroid dose cannot be reduced.

Thiopurines (e.g. azathioprine or mercaptopurine)
Methotrexate
Biologics (e.g. infliximab or adalimumab)

Maintaining remission
Maintenance is tailored to the individual based on side effects, disease severity and patient wishes. This might involve no medications.
First-line agents to maintain remission include:

Azathioprine
Mercaptopurine

Methotrexate can be used in patients who required it to induce remission.
Surgical management
Indications for surgical management of Crohn’s disease include:10

Patient choice: patients with ileocaecal disease may be offered medicines or surgery
Failure of medical management: medications do not improve disease activity or are not suitable
Development of implications: strictures, abscesses, fistulas, obstruction or perforation

Common surgical management options for Crohn’s disease include:10

Strictureplasty: widens narrowed areas of the bowel that could lead to obstruction
Fistula removal: closes, opens, drains or removes a fistula that doesn’t heal with medications
Abscess drainage
Colectomy: removes diseased colon, sparing the rectum
Proctocolectomy: removes diseased colon and rectum
Ileostomy/colostomy
Bowel resection: removal of the diseased small or large bowel and connection of the two healthy ends

Figure 4. A resected jejunum in a patient with known Crohn’s disease, demonstrating a prominent cobblestone appearance.

Complications
Complications of Crohn’s disease include:11

Psychosocial impact (e.g. on school, work or leisure)
Intestinal complications: strictures, fistulas, dilatation, perforation and haemorrhage
Perianal disease 
Anaemia
Malnutrition, faltering growth or delayed pubertal development
Cancer of the small and large intestine

Key points

Crohn’s disease is a form of inflammatory bowel disease that can affect the entire gastrointestinal tract, from mouth to anus.
Some common risk factors include cigarette smoking and NSAID usage.
The most common symptoms include abdominal pain, diarrhoea and weight loss; these may be accompanied by systemic features such as fever and fatigue.
Initial investigations include blood tests (e.g. FBC, iron studies, serum B12 and folate), stool samples (e.g. faecal calprotectin) and imaging.
A diagnosis is usually confirmed after a colonoscopy and biopsies.
Key features on endoscopy and histology include a cobblestone appearance, skip lesions, transmural inflammation and lymphoid hyperplasia.
Management aims to induce and maintain remission. This is usually done via medical management (e.g. corticosteroids, aminosalicylates, thiopurines or biologics); some patients may also require surgery and additional non-medical treatments such as enteral nutrition.
Complications include perianal disease, bowel obstruction, malnutrition and cancer.

Reviewer
Dr Sarah Hyde
Gastroenterology registrar

Editor
Dr Chris Jefferies

References

BMJ Best Practice. Crohn’s disease. Published in 2023. Available from: [LINK]
Ian Wilkinson. Handbook of Clinical Medicine: Crohn’s Disease. Published in 2017. Available from: [LINK]
Crohn’s & Colitis Foundation. Causes of Crohn’s Disease. Published in 2023. Available from: [LINK]
NICE. Crohn’s disease. Published in 2020. Available from: [LINK]
NICE. Crohn’s disease: What are the extra-intestinal manifestations of Crohn’s disease?. Published in 2020. Available from: [LINK]
Maksim. Aphthous Ulcer. License: [CC BY-SA]
Community Eye Health. Acute anterior uveitis. License: [CC BY-NC]
Medicalpal. Erythema nodosum. License: [CC BY-SA]
NICE. Crohn’s disease: management. Published in 2019. Available from: [LINK]
WebMD. Surgery for Crohn’s Disease. Published in 2023. Available from [LINK]
NICE. What are the complications? Published in 2020. Available from: [LINK]

 

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