Crohn’s and Ulcerative Colitis

What are Crohn’s disease and Ulcerative Colitis?

Crohn’s disease and ulcerative colitis are chronic autoimmune conditions that result in inflammation and damage to the digestive tract. While they are both types of ‘inflammatory bowel disease’ (IBD), Crohn’s disease can occur anywhere in the digestive tract while ulcerative colitis affects only the colon (large bowel).

What is the cause of Crohn’s Disease and Ulcerative colitis?

Despite extensive research, the exact cause of the inflammation is still unknown. However, we do know that several key factors play a role.

  • Immune tolerance: The food in Western society is very clean, and children are not exposed to the same amount of bacteria.  Our immune system is unable to tell the difference between good and bad bacteria.  In Crohn’s and colitis, our immune system begins attacking the good bacteria in our digestive tract, causing a continuous inflammation that will often go on for years (1)
  • Genetics: Crohn’s and Ulcerative colitis runs in families. Children of a parent with Crohn’s and Ulcerative colitis have a 21x increased risk of Crohn’s (2) and a 15X increased risk of ulcerative colitis (3).  Crohn’s and Ulcerative colitis is also found in different degrees in different populations in which people with European decent are at the highest risk followed by people of African descent and with Asian descent individuals being at the lowest risk (4).
  • Food: People with Crohn’s and Ulcerative colitis that followed an elemental diet (food broken down to its simplest form) had a 71% remission rate after 4wks (5). This inflammation often returns when they go back on a regular diet.  No one knows exactly why this diet works, but the most widely accepted explanation is that complex foods in the Western diet stimulate the immune system to act inappropriately against the gut.  Some studies point to high amounts of fat in the Western diet (6).
Crohn's Disease

What are the symptoms and complications of Crohn’s and Ulcerative Colitis?

While there is some variation between Crohn’s disease and Colitis, the most common symptoms include:
Abdominal pain – often ‘cramping’ in nature and relieved with passing a bowel motion
Diarrhoea, often containing blood
Nausea and sometimes vomiting
Poor appetite and weight loss
Fatigue

Diarrhoea is the middle of the night is seen with Crohn’s and Ulcerative colitis and is rarely seen in conditions like irritable bowel syndrome (IBS).

The blood will often be mixed inside the stool and sometimes will look black. Black stools are associated with bleeding higher up in the digestive track. Black stools are the result of bacterial digestion of blood.

Crohn’s disease and Ulcerative colitis can be associated with additional complications:
abscess formation
fistula – these are ‘false tracts’ connecting the bowel to other organs like the bladder.
Strictures – these are areas of scaring or narrowing of the bowel which can cause a partial or complete of the digestive tract blockage.

Finally, Crohn’s or Ulcerative colitis can affect areas outside the bowel such as the eyes, skin and joints. These symptoms can occur prior to the development of bowel symptoms.

How do you diagnose Crohn’s and Ulcerative Colitis?

The most accurate way to diagnose Crohn’s and Colitis is with gastroscopy and/or colonoscopy. These procedures allow direct visualization of the inside of the digestive tract to assess for inflammation and damage. Biopsies (tiny samples) can also be taken which allow for microscopic assessment of the lining of the bowel wall.

Radiological tests such as intestinal ultrasound, MRI or CT scan (enterography), can also provide useful information regarding the location, extent and severity of the affect bowel. Furthermore they are invaluable in assess for complications.

Faecal calprotectin is a non-invasive stool test that is being used more and more often to assess the amount of active inflammation in the bowel. It is particularly useful both when obtaining an initial diagnosis and for monitoring the response to treatment.

What is the treatment for Crohn’s and Ulcerative colitis?

The current treatment for Crohn’s and Ulcerative colitis focuses on treating flares and reducing the risk of chronic complications.  If the inflammation can stop and the digestive tract is brought back to normal, the risk of chronic complications is minimized.

The 4 categories of medications for Crohn’s and colitis Ulcerative are:

1. Steroids
2. 5-ASA agents
3. Immunomodulators
4. Biologics

1- Steroids:

Steroids are used to treat Crohn’s or Ulcerative colitis flares (induce remission).  Steroids will often be given intravenously (IV) while in hospital and orally (prednisolone) when outside the hospital.  Steroids have many side effects.  Short term effects include anxiety, insomnia, nausea, headaches, weight gain, and muscle weakness.  Long term serious side effects can be serious as they include diabetes, glaucoma, cataracts, osteopenia, and gastric ulcers.  There are 2 newer steroids (Entocort and Cortiment) that work locally in the gut with minimal side effects.

2- 5-ASA agents:

These medications are used in the treatment of mild to moderate Ulcerative colitis. Some doctors use these medications in Crohn’s however there is minimal evidence that they actually work in Crohn’s (7).  5-ASA meds are well tolerated, but they only work in milder disease.

3- Immunomodulators:

These medications work by suppressing the immune system both systemically and locally in the digestive tract.  The 3 main medications of this group are Azathioprine, 6-Mercatopurine, and Methotrexate.  Their effect at reducing inflammation is overall good, but many patients do not tolerate these medications (nausea, headaches, and general malaise).  As these medications can cause toxicity of the bone marrow and liver, they need to be monitored closely. 

4-Biologics

These are the newest and most effective medications in the treatment of Crohn’s and Ulcerative colitis.  They are synthetic antibodies that bind to a receptor/protein involved in the inflammation pathway.  By blocking a particular receptor or protein in the inflammation pathway, inflammation in the gut is significantly reduced. These medications have minimal side effects and have a good safety profile.  They are reserved for ‘severe’ disease or when other medications have not been helpful.

The biologics include (divided by their mechanism of action):

– TNF alpha blockers: Infliximab (Inflectra/Remicade), Golimumab (Simponi), Adalimumab (Humira)

– IL-12/IL-23 blockers: Ustekinumab (Stelara)

– Alpha-4/Beta-7 blockers: Vedolizumab (Entyvio)

– Jak inhibitor: Tofacitinib (Xeljanz)

Faecal Transplant:  There is now considerable evidence that modifying the gut microbiome is efficacious in bringing colitis under control. Faecal transplant involves taking a small amount of processed stool from a healthy donor and ‘transplanting’ it into the colon of someone with active colitis. Currently, there are 4 randomized control trials (RCTs) that show faecal transplant is an effective treatment for ulcerative colitis. One of the key advantages with faecal transplant is that immune suppressing medications can be avoided. 

The treatment of Crohn’s disease and Ulcerative colitis is complex and should be tailored specifically to an individual’s disease type, location, extent and personal preference.

Ref:

  • Alhagamhmad MHDay ASLemberg DALeach ST. An overview of the bacterial contribution to Crohn disease pathogenesis. J Med Microbiol. 2016 Oct;65(10):1049-1059. doi: 10.1099/jmm.0.000331. Epub 2016 Aug 8.
  • Monsén U, Bernell O, Johansson C, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with Crohn’s disease. Scand J Gastroenterol. 1991;26:302–306.
  • Monsén U, Broström O, Nordenvall B, Sörstad J, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis. Scand J Gastroenterol. 1987;22:214–218.
  • Nguyen GC, Torres EA, Regueiro M, et al. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. 2006;101:1012–1023.
  • Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T, Matsumoto K Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis. 2005 Jun; 11(6):580-8.
  • Gassull MA, Fernández-Bañares F, Cabré E, Papo M, Giaffer MH, Sánchez-Lombraña JL, Richart C, Malchow H, González-Huix F, Esteve M, Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn’s disease: results of a double blind randomised multicentre European trial.  Eurpoean Group on Enteral Nutrition in Crohn’s Disease. Gut. 2002 Aug; 51(2):164-8.
  • Williams, C, Panaccione R, Ghosh S, Rioux K. Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease Therap Adv Gastroenterol. 2011 Jul; 4(4): 237–248.