Lecture 6.1: Inflammatory Bowel Disease (IBD) Flashcards
What are the 2 Types of Inflammatory Bowel Disease?
Ulcerative Colitis and Crohn’s
Causes of Bowel Inflammation: INVITED MD
- Infection
- Neoplasia
- Vascular
- Inflammatory
- Trauma
- Endocrine
- Drugs
- Metabolic
- Degenerative
Types of Colitis (4)
- IBD
- Microscopic Colitis
- Radiation Colitis
- Infectious Colitis
Types of Microscopic Colitis (2)
- Lymphocytic Colitis
- Collagenous Colitis
Causes of Microscopic Colitis
- Medication- e.g. PPIs/ NSAIDs, statins, SSRIs
- Autoimmune disease- e.g Rheumatoid Arthritis, coeliac
disease, psoriasis
When does Radiation Colitis develop?
Develops 6 months to 5 years post regional radiotherapy
What can cause Infectious Colitis?
- Viral, parasitic or bacterial infection
- E Coli and Salmonella are common causes
- C Difficile – often antibiotic induced
Histological Features found in Crohn’s but not in UC (5)
- Granulomas
- Deep Fissuring Ulcers
- Transmural Lymphoid Aggregates
- Small Intestine Involvement
- Crypt Abscesses
What is the Cardinal Symptom of UC?
Bloody diarrhoea
What part of the GI is involved in UC?
Affects mucosa of colon and rectum only
What part of the GI is involved in Crohn’s?
- May involve any part of the GI tract from mouth to
anus - Perianal disease – abscess, fistula
- May be transmural
Extra-Intestinal Manifestations (EIMs) of IBD: CLUECLUE
- Clubbing
- Large joint arthritis
- Ulcers (pyoderma gangrenosum)
- Erythema nodosum
- Cholangitis (primary sclerosing cholangitis)
- Lower back arthritis
- Ulcers (aphthous ulcers in mouth)
- Eye signs e.g. acute uveitis
What IBD is more common?
UC is up to 2-fold more common than Crohn’s disease
What is seen at Colonoscopy for UC?
Continuous inflammation from the rectum
What is seen at Colonoscopy for Crohn’s? (2)
‘Cobble-Stoning’
‘Skip Lesions’
What is the name for inflammation of the lining of the rectum?
Procitis
What is the name for inflammation of the entire colon?
Pancolitis
What imaging is done to help diagnose IBD?
- CT/MRI enterography can be used to visualise the
small bowel - MRI Pelvis to assess known/ suspected peri-anal
Crohn’s disease - AXR (historically)
CD vs UC: Mucosal Involvement
CD: Discontinuous
UC: Continuous
CD vs UC: Aphthous Ulcers
CD: Common
UC: Rare
CD vs UC: Surrounding Mucosa
CD: Relatively Normal
UC: Abnormal
CD vs UC: Longitudinal Ulcer
CD: Common
UC: Rare
CD vs UC: Cobble Stoning
CD: In severe cases
UC: No
CD vs UC: Mucosal Friability
CD: Uncommon
UC: Common
CD vs UC: Vascular Pattern
CD: Normal
UC: Disorted
CD vs UC: Transmural Inflammation
CD: Yes
UC: Uncommon
What factors are involved in the Pathophysiology of IBD?
- Genetics
- Environment
- Diet
- Smoking
- Stress
- Microbial Factors
- Immune Factors
What are pANCA autoantibodies?
Antibodies that stain the material around the nucleus of a neutrophil
In what IBD are pANCA autoantibodies seen?
UC
Management of IBD (7)
- Amino Salicylates
- Corticosteroids
- Antibiotics
- Immunosuppressants
- Biological Therapy
- Surgery
- Avoid NSAIDs
Examples of Amino Salicylates (2)
- Mesalazine
- Sulfasalazine
What IBD are Amino Salicylates used to treat?
To induce remission or to maintain remission of mild to moderate UC
How do Amino Salicylates help manage IBD?
MOA is unclear butut believed to act by activating a class of nuclear receptors involved in the control of inflammation, cell proliferation, apoptosis and metabolic function
When should Amino Salicylates be avoided?
If aspirin allergy
Side-Effects of Amino Salicylates (3)
- Renal Impairment
- Diarrhoea
- Hepatitis
Examples of Corticosteroids (2)
- Prednisolone
- Budesonide
What IBD are Corticosteroids used to treat?
To induce remission of active disease in both UC and CD
How do Corticosteroids help manage IBD?
Potent anti-inflammatories through transcription modulation of genes involved in inflammation
Side-Effects of Corticosteroids (6)
- Significant so ideally not used long term
- Weight Gain
- Hypertension
- Glucose Impairment
- Osteoporosis
- Adrenal Suppression
- Mood Disturbance
When are Antibiotics used to help manage IBD?
Treatment of septic complications and can reduce perianal fistula symptoms
Which antibiotics are shown to have effect in colonic CD? (2)
Metronidazole +/- Ciprofloxacin
Examples of Immunosuppressants or DMARDs (3)
Thiopurines:
* Azathioprine
* Mercaptopurine
* Methotrexate
What IBD are Immunosuppressants or DMARDs used to treat?
To treat refractory or chronic active IBD both UC and CD
How do Immunosuppressants or DMARDs help manage IBD?
- Not really understood but reduce inflammation
- Used as steroid-sparing agents to maintain remission
Side-Effects of Immunosuppressants or DMARDs (2)
- Hepatoxic
- Bone Marrow Toxicity
What are the Types of Biological Therapies to help manage IBD? (4)
- Anti-TNF Therapy
- Ustekinumab
- Vedolizumab
- JAK Inhibitors
What IBD is Anti-TNF Therapy used to treat?
To induce remission in moderate to severe UC and
maintenance of remission for UC and CD
Examples of Anti-TNF Therapy Drugs? (2)
- Infliximab
- Adalimumab
What is the MOA of Anti-TNF Therapy Drugs?
- TNF-α is a chemical messenger (cytokine) and a key
player in the inflammatory process involved in IBD - Infliximab and Adalimumab are monoclonal antibodies
targeting TNF-α - They block the interaction of TNF α with its receptors
- They bind to TNF-α and preventing it from binding to
receptors involved in the inflammatory process
Side-Effects of Anti-TNF Therapy Drugs (2)
- Opportunistic infections
- Anaphylaxis
What IBD is Ustekinumab used to treat?
Maintenance of remission in UC and CD
What is the MOA of Ustekinumab?
Blocks interleukin IL-12 and IL-23 which activate certain
T-cells
Side-Effects of Ustekinumab (6)
- Dizziness
- Sore Throat
- Arthralgia
- Headaches
- Nausea
- Soreness around injection site
What IBD is Vedolizumab used to treat?
Maintenance of remission in CD and UC
What is the MOA of Vedolizumab?
- Binds to ɑ4β7 integrin, a mediator of GI.
inflammation - Decreasing inflammation in the GI tract by blocking
the entry of inflammation- stimulating lymphocytes
Side-Effects of Vedolizumab (6)
- Nasopharyngitis
- Upper Respiratory Tract Infections
- Arthralgia
- Headache
- Fatigue
- Pyrexia
What IBD are JAK Inhibitors used to treat?
To induce remission in moderate to severe UC and
maintain remission in UC
Examples of JAK Inhibitors (2)
- Tofacitinib
- Upadacitinib
What is the MOA of JAK Inhibitors?
- Limit the action of Janus kinase enzymes
- Block cytokines from attaching to receptors in the JAK-
STAT pathway - This reduces the amount of inflammation the immune
system produces
Side-Effects of JAK Inhibitors (6)
- Nausea
- Indigestion
- Diarrhoea
- Headaches
- Upper Respiratory Tract Infection
- Increased Cholesterol Levels
What should be avoided when taking JAK Inhibitors?
Avoid grapefruit juice as it may enhance the therapeutic
effect and increase risk of side effects
What Surgeries can be done to manage CD? (4)
- Colectomy
- Segmental resection
- Stricturoplasty
- Perianal abscess or fistulae
What Surgeries can be done to manage UC? (2)
- Colectomy
- Proctocolectomy
What percentage of UC patients will need surgery in their lives?
20%
What percentage of CD patients will need surgery in their lives?
80%
Complications of IBD (5)
- Primary Sclerosing Cholangitis (PSC)
- Colorectal Cancer
- Strictures in CD
- Fistulae in CD
- Toxic Megacolon
What gene is strongly associated with a big family of rheumatic diseases called spondyloarthropathies?
HLA-B27
What diseases are associated with HLA-B27? (6)
- Inflammatory Bowel Disease (IBD)
- Eye Inflammation Uveitis
- Ankylosing Spondylitis (AS)
- Axial Spondyloarthritis
- Axial Psoriatic Arthritis
- Reactive Arthritis
