Background Information

Definition

Crohn’s disease is a chronic, relapsing-remitting, non-infectious inflammatory disease of the GI tract:

• Characterised by transmural inflammation
• That can affect any part of the GI tract from mouth to anus
• Associated with skip lesions (non-continuous disease)

Risk Factors

Risk factors: ^[Ref]

• Family history
• Smoking (NB the risk of Crohn’s disease is increased in smokers, but the risk of ulcerative colitis is decreased in smokers)
• Genetic predisposition
  • HLA-B27 association
  • NOD2 gene mutation
• NSAIDs may increase the risk of relapse or exacerbation

Clinical Manifestation

Crohn’s disease typically present as a chronic intermittent course, with episodic acute flares and periods of remission.

GI manifestations	Chronic diarrhoea (lasting >4 weeks) Classically non-bloody diarrhoea But Crohn’s colitis may cause bloody diarrhoea and other overlapping symptoms as ulcerative colitis (e.g. faecal urgency, tenesmus) Nocturnal diarrhoea can occur Abdominal pain (classically RIF pain – due to ileal involvement) Palpable RIF mass (due to ileal inflammatory swelling)
Extra-GI manifestations	Extra-GI symptoms are common in Crohn’s colitis and may present BEFORE GI symptoms become prominent. Non-specific constitutional symptoms (e.g. fever, fatigue, malaise, anorexia) Joints Clubbing Enteropathic arthritis (type of seronegative spondyloarthropathies) Pauci-articular arthritis – most common extra-GI feature Polyarticular arthritis Axial arthritis Oral aphthous mouth ulcers (more common in Crohn’s disease than ulcerative colitis) Aphthous ulcers are common and many people get it Ulcers that doesn’t heal >3 weeks are suspicious (it could be malignancy or IBD)  Eyes Uveitis Episcleritis Skin Erythema nodosum Pyoderma gangrenosum Psoriasis
Complications	Intestinal complications Strictures (can cause bowel obstruction) Perianal disease (fissures / fistulae / abscesses) ↑ Risk of colorectal cancer Fistulae (most common: perianal fistulae, also entero-cutaneous, entero-vesical, entero-vaginal) Malabsorption Osteoporosis – common (also from the steroid treatment, smoking status etc. apart from malabsorption) Anaemia (from iron deficiency / B12 deficiency / folate deficiency / anaemia of chronic disease) ↑ Risk of gallstones (due to malabsorption of bile acid in the ileum, causing a relative increase in cholesterol concentration in bile) ↑ Risk of calcium oxalate renal stones Malnutrition / faltering growth / delayed pubertal development (in children)

Prognosis

Crohn’s disease is a lifelong condition that can significantly impair quality of life:

• Only ~10% patients achieve prolonged clinical remission
• ~20% patients are admitted to hospital per year
• ~50% patients underwent surgery within 10 years of diagnosis
• ~50% patients who underwent surgery had recurrence within 10 years of diagnosis

Diagnosis

Work Up

NICE CKS recommends the following tests when Crohn’s disease is suspected. There are 2 main purposes of the following tests: 1) to support the diagnosis of IBD and 2) to exclude differential diagnoses.

Category	Test	Purpose / Interpretation
Blood tests	FBC	Anaemia is common at diagnosis, supports malabsorption, malnutrition, GI bleed ↑ Platelet count suggests inflammation
	U&E
	LFT, including albumin	↓ Albumin may indicate inflammation and malnutrition, or possible protein-losing enteropathy
	Serum ferritin, vitamin B12, folate, vitamin D	Detect nutritional deficiencies due to malabsorption
	Inflammatory markers (CRP and ESR)	↑ Inflammatory markers suggest inflammation
	Coeliac serology	Exclude coeliac disease
Stool tests	Stool microscopy and culture (including C. difficle toxin)	Exclude infective gastroenteritis or pseudomembranous colitis (C. difficle infection) Note that the presence of infection does not exclude Crohn’s
	Faecal calprotectin	↑ Faecal calprotectin suggests inflammation

Some other tests:

• TFT – hyperthyroidism can cause diarrhoea
• Serology (note that it has limited role in diagnosing IBD but can be asked in exams)
  • ↑ pANCA
  • ↑ ASCA

Ileocolonoscopy

Ileocolonoscopy with biopsy of both involved and uninvolved mucosa is the gold standard diagnostic test for Crohn’s disease

• It is essential that the procedure reaches the terminal ileum (i.e. beyond the ileocaecal valve) and includes biopsies from this region, since ileal involvement is very common in Crohn’s disease.
• For this reason, the procedure is specifically termed ‘ileocolonoscopy’ rather than colonoscopy alone.

Category	Crohn’s Disease	Ulcerative Colitis
Macroscopic Findings	Distribution / location: Skip lesions – discontinuous pattern of involvement Ileum involvement almost always present Rectal sparing is common Appearance: Shallow ulcers (aphthous ulcers) Cobblestone appearance (inflamed sections interspread with deep ulcerations that resemble cobblestones) Strictures	Distribution / location: Continuous inflammation Rectal involvement almost always present Rarely extend proximal to the ileum Appearance: Friable mucosa with bleeding on contact Pseudopolyps (raised areas of normal mucosa from repeated ulceration and healing)
Histology Findings	Transmural inflammation (full-thickness involvement) Non-caseating granulomas (specific but not always present) Increase in goblet cells	Mucosal / submucosal inflammation Crypt abscesses Absence of granulomas Reduced  goblet cells

Imaging

Imaging is essential for diagnosis in Crohn’s disease, as Crohn’s tends to affect any part of the GI tract, especially the small bowel, which is not visualised by ileocolonoscopy.

Imaging modality	Findings
Cross-sectional enterography (CT / MR)	Mesenteric fat stranding (suggests transmural inflammation) Excessive mesenteric fat around the affected bowel segment (Creeping fat sign) Intestinal wall oedematous thickening Can also identify complications like strictures, fistula, abscesses
CT AP with IV contrast	Usually only used in acutely unwell patients who cannot tolerate oral contrast
Small bowel follow-through (with barium contrast)	Fistula Bowel narrowing (string sign)

Management

Inducing Remission

Step 1

Management in adults:

1st line	Conventional systemic corticosteroid  IV methylprednisolone or hydrocortisone / oral prednisolone (usually reserved for mild flares, for outpatient management) Conventional steroids are the most effective in inducing remission
2nd line	Budesonide (oral) monotherapy (less effective but fewer side effect)
3rd line	Aminosalicylate monotherapy (e.g. mesalazine, sulfasalazine)

In children / young people, exclusive enteral nutrition is the preferred method to induce remission, to avoid use of corticosteroids (esp. when growth or steroid side effects are a concern)

• Exclusive enteral nutrition involves a nutritionally complete liquid diet, excluding regular foods, typically given for 6–8 weeks
• It induces remission by supporting nutritional needs, modifying the microbiome and immune response, protecting the gut barrier, and eliminating harmful dietary triggers

Step 2

Add-on therapy is indicated if:

• Steroid dose cannot be tapered, or
• ≥2 exacerbations in 1 year (despite on steroids)

Add-on drugs (to be added onto the corticosteroid but NOT as monotherapy):

• 1st line: azathioprine / mercaptopurine
• 2nd line: methotrexate

Step 3

Consider TNF–α inhibitor if there is no response to conventional therapy:

• Infliximab / adalimumab monotherapy or combined with an immunosuppressant

Step 4

Consider:

• Ustekinumab (IL12, 23 inhibitor), or
• Vedolizumab (anti-α4β7)

Maintaining Remission

It is very important to advise on smoking cessation (reduces risk of flares)

 

Offer patient to choose between receiving and not receiving maintenance treatment.

Maintenance Treatment

If maintenance treatment is decided:

• 1st line: azathioprine / mercaptopurine
• 2nd line: methotrexate

Do not offer steroids to maintain remission.

Colonoscopic Surveillance

Perform a baseline colonoscopy with chromoscopy and biopsy of any abnormal areas to assess risk of developing colorectal cancer

In Crohn’s disease, only those with Crohn’s colitis involving >1 segment of colon need ongoing colonoscopic surveillance

• Such that those with predominant small bowel disease and limited large bowel disease does NOT need colonoscopic surveillance
• Unlike in ulcerative colitis, where most patients need colonoscopic surveillance, apart from those with isolated proctitis

References