QuestionSBA
QuestionChoice
Irritable bowel syndrome may present with similar symptoms, which can become worse in periods of stress. However, the histology findings point towards an inflammatory cause
32920
c
Irritable bowel syndrome
QuestionChoice
Serositis is absent in most ulcerative colitis histology, except in fulminant colitis and granulomas are absent, except in the case of ruptured crypts. Ulcerative colitis is more likely to present with bloody diarrhoea and colicky abdominal pain, urgency and tenesmus
32919
b
Ulcerative colitis
QuestionChoice
Anxiety may present with abdominal pain, which is sometimes described as "churning". However, it will not lead to the histological findings seen in this patient
32921
d
Anxiety
QuestionChoice
Coeliac disease is likely to show subtotal villus atrophy on histology rather than serositis and granulomas. Serological testing whilst the patient is having gluten in their diet is usually done before biopsies
32922
e
Coeliac disease
QuestionChoice
The histology is highly specific for Crohn's disease. Serositis and granulomas are often present in Crohn's, whereas they are absent in ulcerative colitis. Crohn's disease can present with variable symptoms, including diarrhoea, which may or may not contain blood, as well as generalised abdominal pain
32918
a
Crohn's disease
Concept
Chapter
# Summary

Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease (IBD) characterized by transmural granulomatous inflammation. Key signs and symptoms include gastrointestinal and systemic symptoms, such as crampy abdominal pain, diarrhoea, weight loss, and fever. The disease is diagnosed primarily through blood tests and endoscopy with imaging. Management strategies include monotherapy with glucocorticoids, azathioprine, mercaptopurine, and biological agents for severe cases. Surgical management is rarely curative and should be maximally conservative.

# Definition

Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease (IBD). It is characterised by transmural granulomatous inflammation which can affect any part of the gastrointestinal tract ('from mouth to anus', most commonly the terminal ileum, leading to fistula formation or stricturing.

# Aetiology

The exact cause is unknown, but it is thought to be an inappropriate reaction to gut flora in a susceptible person. Important risk factors include:

- Family history - 10-25% of patients have a first-degree relative who also suffers from Crohn's disease
- **Smoking** - x3 increased risk
- Diets high in refined carbohydrates and fats have been implicated

# Epidemiology

In Europe the incidence of Crohn's disease is 5.6 per 100, 000 at ages 15-64. The disease is more common in northern climates and developed countries. In the last 60 years the incidence of Crohn's disease has increased in Europe and North America, and is now approximately equal to that of ulcerative colitis.

Crohn's disease has a bimodal age of onset: the most common age of onset is between 15 and 40 years old, but there is a smaller secondary peak between 60-80 years.

Crohn's disease is more common in Caucasian people than in Asian and black people. Ashkenazi Jews have a 2-4 fold higher risk of Crohn's disease.


# Signs and Symptoms

Symptoms: 

- Gastrointestinal symptoms (crampy abdominal pain and non-bloody diarrhoea)
- Up to 50% have perianal disease
- Systemic symptoms (weight loss and fever)

Signs: 

- General appearance: cachectic and pale (secondary to anaemia), clubbing.
- Abdominal examination: aphthous ulcers in the mouth, right lower quadrant tenderness and a right iliac fossa mass.
- PR examination to check for perianal skin tags, fistulae, or perianal abscess.

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**Extra-gastrointestinal manifestations include:**

Dermatological manifestations:

- Erythema nodosum (painful erythematous nodules/plaques on the shins)
- Pyoderma gangrenosum (a well-defined ulcer with a purple overhanging edge)

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Ocular manifestations:

- Anterior uveitis (painful red eye with blurred vision and photophobia)
- Episcleritis (painless red eye).

Musculoskeletal manifestation:

- Enteropathic arthropathy (symmetrical, non-deforming)
- Axial spondyloarthropathy (sacro-iliitis), 

Hepatobiliary manifestations:

- Gallstones (these are more common in Crohn's disease than in ulcerative colitis) - reduced bile acid reabsorption and increased calcium loss predisposes to gallstones

Haematological and renal manifestations:

- AA amyloidosis (secondary to chronic inflammation) and renal stones (more common in Crohn's disease than in ulcerative colitis)

# Investigations 

- Bedside:
	- Stool culture is necessary to exclude infection (MC&S and ovas/cysts/parasite).
	- **Faecal calprotectin** (an antigen produced by neutrophils) will be raised (this helps distinguish inflammatory bowel disease from irritable bowel syndrome).

- Blood tests:
  - Raised white cell count
  - Raised ESR/CRP
  - Thrombocytosis
  - Anaemia (secondary to chronic inflammation)
  - Low albumin (secondary to malabsorption)
  - Haematinics and iron studies including (B12, folate) due to terminal ileum involvement


- Imaging:
	- Endoscopy with imaging is required for diagnosis. Small bowel video capsule endoscopy can be used for proximal disease
	- MRI can be used for suspected small bowel disease.
	- Upper GI series may show the 'string sign of Kantour'. This is used to describe the string-like appearance of contrast-filled narrowed terminal ileum, and is suggestive of Crohn's disease.
	- Colonoscopy with biopsy will reveal:
		- Intermittent inflammation **('skip lesions')**
		- Cobblestone mucosa (due to ulceration and mural oedema)
		- Rose-thorn ulcers (due to transmural inflammation), ± fistulae or abscesses.
		- Non-caseating granulomas

# Management

- As a general management point, it is paramount to advise patients with Crohn's who are smokers to **stop smoking** as this is known to strongly impact disease activity

## Inducing remission

- The first step of treatment is inducing remission in patients having a flare
- Patients should be offered monotherapy with glucocorticoids (oral prednisolone, or IV hydrocortisone if first presentation is severe flare necessitating admission).
- There is an increasing role for biologics for acute management of severe flares

## Maintaining remission

- Azathioprine or mercaptopurine may be added on to induce remission if there are 2 or more exacerbations in a 12-month period or the glucocorticoid cannot be tapered.

  - It is important to assess for thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine. If there is underactivity, this greatly increases the risk of profound bone marrow suppression if the above medications are given

- Methotrexate may be considered in patients who are intolerant/have a contraindication to azathioprine or mercaptopurine or who do not respond to azathioprine or mercaptopurine monotherapy.
- Biological agents (such as infliximab or adalimumab) are recommended in patients with severe Crohn's disease who fail to respond to the above.
	- These patients should have a CXR before treatment initiation due to the risk of re-activation of latent TB


## Surgical management

Surgical management is rarely curative in Crohn's disease (unlike in ulcerative colitis) because disease can occur anywhere along the GI tract, however 50-80% of Crohn’s patients end up requiring surgery at some point.

Surgical options will depend on the part of the GI tract that is affected, and is indicated in those who have failed medical therapy or in those with severe stricturing or fistulating disease:

-	Control fistulae 
-	Resection of strictures
-	Rest/defunctioning of the bowel


### Management of peri-anal fistulae

- Drainage seton is the management of choice for high (trans-sphincteric) fistulae. A seton is a thread passed through the fistula tract, forming a ring between the internal and external openings. It is used in the management of high trans-sphincteric fistulae, to prevent division of the anal sphincter muscles and incontinence. Closure of the fistula occurs by the formation of granulation tissue.
- Fistulotomy is the management of choice for low (submucosal) fistulae. Fistulotomy involves dissecting the superficial tissue and opening the fistula tract. This is not a treatment option for high fistulae due to the risk of incontinence.
- 'Sphincter saving' methods include fibrin glue and fistula plug - these are still under investigation and have not yet been approved in mainstream management.

### Management of peri-anal abscess

- The patient should be started on intravenous antibiotics e.g. ceftriaxone + metronidazole.
- Patients typically require examination under anaesthetic and incision and drainage. An incision is made in the affected region, the pus is broken up, the infected tissue material is excised, and anti-septic soaked packs are inserted. Healing occurs by secondary intention.

# Complications

- **Fistulas:**
  - Formation of abnormal connections between different parts of the digestive tract or between the digestive tract and other organs.
  - Commonly involves the small intestine and other structures like the bladder or skin.

- **Strictures:**
  - Narrowing or tightening of the intestinal walls.
  - Can lead to bowel obstruction and difficulties with the passage of stool.

- **Abscesses:**
  - Collection of pus within the abdomen, often near areas of inflammation.
  - Presents with localized pain, swelling, and may require drainage.

- **Malabsorption:**
  - Impaired absorption of nutrients due to inflammation and damage to the intestinal lining.
  - Can lead to nutritional deficiencies and weight loss.

- **Perforation:**
  - Formation of a hole or tear in the intestinal wall.
  - Can result in peritonitis, a serious and potentially life-threatening condition.

- **Nutritional Deficiencies:**
  - Chronic inflammation can affect nutrient absorption.
  - Common deficiencies include vitamin B12, vitamin D, and iron.

- **Increased Risk of Colon Cancer:**
  - Prolonged inflammation may elevate the risk of developing colorectal cancer, particularly in long-standing disease involving the colon.

- **Osteoporosis:**
  - Reduced bone density due to chronic inflammation and corticosteroid use.
  - Increases the risk of fractures.

- **Intestinal Obstruction andToxic Megacolon:**
  - Severe inflammation can lead to the dilation of the colon.
  - Presents as abdominal distension, fever, and can be a medical emergency.


# Comparison with Ulcerative Colitis

Please see below a summary table comparing Crohn's disease and Ulcerative colitis:

| Characteristic                     | Crohn's Disease                       | Ulcerative Colitis                   |
|------------------------------------|---------------------------------------|-------------------------------------|
| **Location**                       | Any part of the digestive tract, from the mouth to the anus (most commonly affects the terminal ileum and colon) | Limited to the colon and rectum      |
| **Inflammation Pattern**           | Patchy, skip lesions                  | Continuous, involves the entire colon|
| **Depth of Inflammation**          | Full thickness (transmural)           | Limited to the inner lining (mucosa and submucosa)|
| **Symptoms**                       | Abdominal pain, non-bloody diarrhoea, weight loss | Bloody diarrhoea, abdominal cramps   |
| **Complications**                  | Fistulas, strictures, abscesses        | Toxic megacolon, colon cancer risk  |
| **Extraintestinal Manifestations** | Joint pain, skin problems, eye inflammation | Joint pain, skin problems, eye inflammation |
| **Endoscopy Findings**             | Cobblestone appearance, deep ulcers   | Continuous colonic inflammation, ulcers |
| **Diagnostic Imaging**             | Transmural inflammation visible on imaging (e.g, MRI) | Limited to the colonic mucosa and submucosa, visible on colonoscopy |
| **Treatment Approach**             | Individualised, may involve medications (e.g. steroids, immunosuppressants) and surgery | Medications (e.g. aminosalicylates, steroids, immunosuppressants), surgery (in severe cases) |
| **Prognosis**                      | Variable, chronic condition with periods of remission and exacerbation | Variable, can be chronic with periods of remission, may require surgery in some cases |


# NICE Guidelines

[Click here to see information on NICE CKS on Crohn's disease](https://cks.nice.org.uk/topics/crohns-disease/)


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An example of pyoderma gangrenosum
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The typical appearance of a mouth ulcer seen in a patient with Crohn's disease.
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An example of erythema nodosum on the shins.
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Histology in Crohn's disease typically shows transmural inflammation, granulomas, crypt abscesses, and mucosal ulceration, often involving any part of the gastrointestinal tract and characterized by skip lesions and fibrosis.
A 21-year-old female presents to her GP because she has been feeling increasingly anxious. She has recently moved house and broken up with her partner. She has also been experiencing intermittent diarrhoea and diffuse abdominal pain. Her GP decides to send her for an ileocolonoscopy where biopsies are taken. These biopsies show granulomas and inflammation of the serous membrane.

What is the most likely diagnosis?
a