The incidence of Crohn’s disease is higher in the Western world (i.e. UK, Europe and America) than the rest of the world. TRUE/FALSE?
TRUE
What can be used to prove that there are genetic links in IBD?
- Twin studies
- Affected 1st degree relatives
What genetic mutation is present in 10-20% of caucasians with Crohn’s disease? What does it cause?
NOD2/ CARD15 (IBD-1)
=> Encodes a protein involved in bacterial recognition
How can adaptive immunity of the mucosa be affected by abnormal T cell function?
Overactive effector T-cells → Inflammation/ Disease
Absence of regulatory T-cells → Uncontrolled Inflammation/ Aggressive Disease
What cells of the adaptive immune system cause Crohn’s disease, and which cause UC?
Crohn's = Th1 mediated UC = Mixed Th1/ Th2 or NKCs
Does smoking aggravate Crohn’s or UC?
Aggravates Crohn’s disease but protects against UC
Describe the typical clinical presentation of UC?
- Female 20-30s
- Relapsing course
- Affects rectum extending proximally
How is UC referred to if it only affects a) the rectum? b) the rectum and left-side of the colon? c) the entire colon?
a) Proctitis
b) Left-sided colitis
c) pancolitis
What symptoms are usually present in UC?
- Diarrhoea + bleeding
- Increased bowel frequency
- Urgency
- Tenesmus (incomplete emptying)
- Incontinence
- Night rising
- Lower abdo pain (esp. LIF)
What should you remember to check in patient’s history if you suspect UC?
- Recent travel
- Antibiotics
- NSAID’s
- Family history
- Smoking
- Skin, eyes, joints
What criteria is used to assess the severity of UC, and why is this scoring important?
Truelove and Witt criteria: >6 bloody stools/24 hour \+ 1 or more of: - Fever (>37.8°C) - Tachycardia (>90/min) - Anaemia (Haemoglobin <10.5g/dl) - Elevated ESR (>30mm/hr)
Important as Severe UC = 30% risk of colectomy
What investigations can be used if you suspect UC?
- C-reactive protein (CRP)
- Albumin (a negative acute phase reactant)
- Plain AXR
- Endoscopy
- Histology
What can an AXR show you that would point towards a diagnosis of UC?
- Stool distribution = Absent in inflammed colon
- Mucosal oedema / ‘thumb-printing’
- Toxic megacolon:
=> Transverse >5.5cm
=> Caecum >9cm
What signs at endoscopy indicate UC is present?
Loss of vessel pattern
Granular mucosa
Contact bleeding
What signs on histology indicate UC is present rather than normal mucosa?
- lack of goblet cells
- crypt distortion
- formation of abscesses (due to crypts closing at surface)
What complications can arise from UC?
Increased risk of colorectal cancer
- depends on severity and extent of disease
What extra-intestinal manifestations are common in UC?
- Skin - erythema nodosum/ pyoderma gangrenosum
- Joint arthritis
- Eyes (uveitis)
- Deranged LFTs, gallstones/ PSC
- Oxalate renal stones
PSC is more commonly associated with UC than Crohn’s. TRUE/FALSE?
TRUE
- 80% of those with PSC have associated IBD
When does Crohn’s disease normally present?
90% onset before age 40
Describe the normal clinical appearance of Crohn’s which distinguishes it from UC?
- Affects any region of GI tract from mouth to anus
=> Skip lesions - Transmural inflammation (all the way through wall)
What peri-anal disease is common in Crohn’s ?
- Recurrent abscess formation
- Pain
- fistula with persistent leakage
- Damaged sphincters
Resections to treat Crohn’s disease are minimised as they are NOT curative. TRUE/FALSE?
TRUE
- many patients require multiple surgeries
What symptoms can patients with Crohn’s disease experience?
Small intestine disease:
- Abdominal cramps (peri-umbilical)
- Diarrhoea
- Weight loss
Colon:
- Cramps (lower abdomen)
- Diarrhoea with blood
- Wt loss
Mouth:
- Painful ulcers
- swollen lips
- angular chielitis
Anus:
- peri-anal pain
- abscess
What may you notice on examination of a patient with suspected Crohn’s disease?
- Evidence of wt loss
- RIF mass
- peri-anal signs
What blood tests would you consider if you suspected Crohn’s disease in a patient?
- CRP
- albumin
- platelets
- B12 (absorbed in terminal ileum)
- ferritin
What is usually visible on Crohn’s histology that distinguishes it from UC?
- granuloma formation common
What investigations can be used to view the small and large bowel lumens in Crohn’s disease?
SMALL:
- Barium follow-through
- MRI
- Technetium-labelled white cell scan
LARGE:
- colonoscopy
What are the aims of treatment in IBD?
- Control inflammation + heal mucosa
- Restore normal bowel habit
- Improve quality of life
- Avoid long-term complications
What lifestyle advice can be given to help treat patients with Crohn’s disease?
- SMOKING aggravates Crohns
=> makes worse disease outcome
=> more rapid recurrence post-surgery
What drug therapies are used in UC?
5ASA (mesalazine)
Steroids
Immunosuppressants (e.g. azathioprine)
Anti-TNF therapy
What drug therapies are used to treat Crohn’s disease?
Steroids
Immunosuppressants (e.g. azathioprine)
Anti-TNF therapy
How do 5ASA therapies (e.g. Mesalazine) work to treat IBD?
- produces a Topical effect
- Anti-inflammatory
- Reduces risk of colon cancer
What are the side effects of using 5ASA therapies?
- diarrhoea
- idiosyncratic nephritis
How are 5-aminosalicylic acid (5ASA) preparations delivered topically to the bowel mucosa?
- suppositories
- enemas
5ASA drugs can also be taken orally. TRUE/FALSE?
TRUE - these may come in granules/ sachets rather than a tablet/capsule form
They can be:
- Prodrugs
- pH dependent release (Asacol)
- delayed release (Pentasa)
Why are different preparations of oral 5ASA agents made?
They act on different areas of the GI Tract
e. g.
- Sulphasalazine only acts on colon
- Asacol acts on ileum and colon
- Pentasa acts on duodenum, jejunum, ileum and colon
What arer the advantages and disavantages of using suppositories or enemas?
- Suppositories coat <20cm BUT have better mucosal adherence than enemas
- Reflex contraction aids proximal spread of enemas
- <10% enemas actually remain in the rectum
What corticosteroids are used to treat IBD and what is the aim of using this treatment?
- Prednisolone: oral / topical
=> short course used to induce remission
- high dose initially, reducing over 6 - 8 weeks
What are the potential side effects of using steroid treatments?
MSK:
- Avascular necrosis
- Osteoporosis
DERM:
- Acne
- Thinning of skin
Metabolic:
- Weight gain
- Diabetes
- hypertension
Others:
- Cataracts
- Growth failure
What immunosuppressants can be used as a more potent suppressor of inflammation in IBD?
- azathioprine / mercaptopurine
- methotrexate
Azathioprine has a slow onset of action. TRUE/FALSE?
TRUE
- 16 weeks
Why should Allopurinol not be co-prescribed with azathioprine?
Allopurinol inhibits Xanthine oxidase
- XO enzyme is involved in the activation of azathioprine to its active product
What are the main side effects of Azathioprine use?
- Pancreatitis
- Leucopaenia
- Hepatitis
- Small risk of lymphoma or skin cancer
What is anti-TNF therapy and how does it work?
Tumour Necrosis Factor α = proinflammatory cytokine
=> this drug provides antibodies to TNF
=> Promote apoptosis of activated T- lymphocytes
How can anti-TNF drugs be delivered?
infliximab; IV
adalimumab; S/C injection
Anti-TNF drugs have a rapid onset of action. TRUE/FALSE?
TRUE
- 30-40% remission after single infusion
When do the NICE guidelines indicate use of anti-TNF alpha in IBD?
- part of long term strategy (inc. immunosuppression, surgery (Crohns), supportive therapy etc)
- Used if refractory / fistulising disease
- (make sure to exclude current infection / TB before use)
What are the two main types of surgery used in IBD?
Emergency
- Failure to respond to medical therapy, small bowel obstruction, abscess, fistulae
Elective
- Failure to respond to medical therapy
- Dysplasia of colon mucosa
Crohn’s surgery is NOT curative. TRUE/FALSE?
TRUE
- minimal resections each time
Repetitive surgery for Crohn’s can result in what clinical outcome?
‘short gut syndrome’
=> May require lifelong total parenteral nutrition (reduced life expectancy)
Surgery for UC is normally curative. TRUE/FALSE?
TRUE
What surgeries can be offered to UC patients?
- Permanent ileostomy
OR - Restorative proctocoloectomy and pouch
What emergency surgeries for IBD are considered “planned”?
- Sub total colectomy for UC
- Resection of Crohn’s disease
Why may a patient with Crohn’s disease undergo elective operations?
- Resection
- Stricturolplasty
- Fistulas
- Anal disease
What elective operations can be done to help with UC?
- Proctocolectomy with end ileostomy
- Proctocolectomy with ileorectal anastomosis
What indications are there for elective surgery in UC?
- Medically unresponsive disease
- Dysplasia/malignancy
- Growth retardation in children
- Attempted resolution of extra-intestinal disease
What different types of ileorectal anastomosis can be created after surgery for UC?
W pouch
J pouch
S pouch
Pouches are usually more popular with younger patients. TRUE/FALSE?
TRUE
- means they don’t have colostomy/ ileostomy bag to change/ wear for the rest of their life
What immediate local complications can occur during IBD surgery?
- haemorrhage
- enterotomy
What early complications can present due to IBD surgery?
- urinary dysfunction
- wound infection/ abscess
- anastomotic leak
- ileus
- portal vein thrombosis
WHat complications of IBD surgery present late?
- impotence
- infertility
- pouchitis
- DVT/PE
- small bowel obstruction
What criteria is used to assess the severity of a UC attack?
Truelove and Witt Criteria
- ESR/PV
- Haemoglobin
- Bloody Stools
- Temperature
- Heart rate
Removal of the colon in IBD tends to settle rectal disease (even though the rectum itself is not removed). TRUE/FALSE?
TRUE
- rectal problems can be managed medically with enemas/ medication
What are the main indications for surgery in Crohn’s disease?
- Stenosis causing obstruction
- Fistulae
- Abscesses
- Bleeding (acute or chronic)
- Free perforation
What surgery can be completed if patients with Crohn’s experience gastro-duodenal disease?
Gastrojejunostomy
- allows to avoid duodenal or pyloric stenosis
Pouches for Crohn’s disease patients is controversial. TRUE/FALSE?
TRUE
Squamous cell carcinoma may occur after peri-anal Crohn’s disease. TRUE/FALSE?
TRUE