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CROHN'S DISEASE

Written by Katie Bloor

Last Reviewed: September 2019

Review Due: September 2020

 

DEFINITION2

‘a chronic inflammatory gastrointestinal disease characterised by transmural inflammation, which may affect any part of the gastrointestinal tract from the mouth to the anus, most commonly affecting the terminal ileum’

 

AETIOLOGY1-3

The aetiology of Crohn’s Disease currently remains unknown, however various factors have been implicated:

  1. Environmental

    • Presumed causative agents include smoking, the oral contraceptive pill and infections such as mycobacterium avium paratuberculosis

  2. Genetic

    • Various genome wide association studies have identified over 70 different genetic susceptibility loci, with the strongest association being between CARD 15 (caspase recruitment domain family, member 15), which encodes the NOD 2 (nucleotide-binding oligomerisation domain containing 2) pathogen recognition protein

SIGNS AND SYMPTOMS2-3

 

PATHOPHYSIOLOGY2,3

As mentioned in the aetiology section, there are aspects of Crohn’s Disease, and it’s mechanisms that remain unknown. However, there are various theories about its pathophysiology, indicating a role for “infectious, immunological, environmental, dietary and psychosocial factors” causing Crohn’s Disease in a genetically and immunologically susceptible person.

Crohn’s and Ulcerative Colitis are both inflammatory bowel diseases and may, at times, have a similar presentation however there are important clinical and pathological differences that distinguish between these two disorders.

 

The list below focuses on the pathological findings of Crohn’s Disease, usually on imaging including; contrast radiological studies, CT/MRI, and endoscopy:

  • Cobble-stoning mucosa and aphthous, or linear ulcers are a characteristic endoscopic appearance.

  • Submucosal oedema, rigidity, or pseudodiverticula; such findings can be found on contrast radiological studies. 

  • Fistulation; chronic transmural inflammation results in a thickened bowel walls, resulting in scarring, luminal formation and stricture formation. This may lead to fistulation, perforation ann/or abscess formation. 

  • Crypt abscesses and granulomas; Crypt abscesses are caused when there is an inflammatory infiltrate surrounding the intestinal crypt, subsequently developing into an ulceration of the superficial mucosa. This inflammatory cascade continues, progressing into the deeper layers of the intestinal walls, causing non-caseating granulomas. 

  • Mucosal discontinuity and transmural involvement.

 

Investigations1-2

BLOOD TESTS

FBC

May show anaemia (due to chronic inflammation, blood loss, or iron malabsorption, and/or malabsorption of vitamin B12 or folic acid), thrombocytosis or leukocytosis. 

U&Es

Findings associated with severe disease include hypocalcaemia and hypomagnesaemia/hypophosphatemia (which can be caused by diarrhoea). 

ESR/CRP

May be elevated (inflammatory markers correlate closely with the activity of Crohn’s Disease). 

LFTs

May demonstrate hypoalbuminemia and hypercholesterolaemia. 

Full Iron Studies

(including serum iron, serum ferritin, total iron-binding capacity (TIBC), transferrin saturation)

Iron deficiency may be associated with gastrointestinal bleeding or malabsorption of iron. The results may be normal or may show changes which are consistent with iron deficiency. 

B12 and Folate

Result may be low, due to malabsorption. 

IMAGING

Colonoscopy and Rectal Biopsy 

(Endoscopy/Colonoscopy with a biopsy is considered the key test in order to diagnose Crohn’s Disease, alongside a relevant clinical history/blood test results)

Small Bowel Enema (to detect ileal disease)

Barium Enema (rarely used)

Shows cobble-stoning, “rose-thorn” ulcers +/- colon strictures

MRI

Can assess pelvic disease and fistulae, and a small bowel MRI can assess disease activity and show sites of strictures

OTHER

Stool Microscopy & Culture and C. Diff Toxin Screen

To exclude Campylobacter, Clostridium Difficile or Escherichia Coli infection

 

TREATMENT1-4

ACUTE FLARES

Mild Attacks - where the patient is symptomatic but systemically well

  • Oral steroids on a reducing course once symptoms have settled

  • Weekly clinic review

Severe Attacks - symptomatic and systemically unwell

  • Admit patient for IV steroids (e.g. hydrocortisone), keep patient nil by mouth, and give IV Fluids 

  • Give oral or IV antibiotics (e.g. metronidazole)

  • Remember to continually monitor patient’s temperature, heart rate, blood pressure and record stool frequency/character on a stool chart

  • Daily physical examination and daily abdominal x-ray. 

  • Daily blood tests including; FBC, U&E, LFTs, CRP and ESR

  • Consider the need for a blood transfusion (if haemoglobin is below locally agreed transfusion threshold)

  • In-patient dietician review (consider elemental diet, or parenteral nutrition)

CHRONIC

The main principle of Crohn's Disease management is inducing and then maintaining remission. Steroids are not appropriate for long-term maintenance therapy; instead they are used to induce remission following a first presentation or managing a single inflammatory exacerbation of the disease within a 12-month period. Patients who have ileocecal, distal ileal or right-sided colonic disease involvement have shown to respond better to the specific steroid budesonide.

Maintenance of Remission

1st Line: Azathioprine or Mercaptopurine (as a monotherapy) are the first-line treatment options for Crohn's Disease, alongside a corticosteroid to induce remission.


2nd Line: Methotrexate can be used to maintain remission, but this is only to be used in patients who are intolerant or are not suitable for Azathioprine or Mercaptopurine.


3rd Line: TNF-alpha inhibitors (Infliximab and Adalimumab)

Surgery

50-80% of patients who suffer with Crohn’s Disease will need at least one operation within their lifetime. Such examples of these surgeries include; colectomy (where the diseased section of colon is removed), bowel resection (removing the damaged portion of intestine), or proctocolectomy (removing the colon and rectum, and creation of a stoma). 

This disease is not curative and can be debilitating for the patient. Indications for surgery include:

  • Drug Failure (most common indication)

  • GI Obstruction from Stricture

  • Perforation

  • Intestinal Obstruction

  • Fistulae

  • Abscess

 
 

EPIDEMIOLOGY1

The highest incidence of Crohn’s Disease is in northern climates and in developed countries, with a lower incidence in Asia and South America. It has also been shown to be more common in Caucasians and Ashkenazi Jews, with an equal prevalence between men and women. The peak age of onset of Crohn’s is between 15 and 40, with a smaller, second peak between 60-80 years.

REFERENCES

  1. British Medical Journal Best Practice. Crohn’s Disease.

  2. Longmore, M, Wilkinson, I.B, Baldwin , A, Wallin, E. Oxford Handbook of Clinical Medicine. (9th ed.). England: Oxford University Press; 2014. pp 274-275

  3. Crohn’s Disease. Hopkins Medicine.

  4. National Institute for Health and Care Excellence. Crohn’s Disease.