tbl 4 clinical: ibd

Question 1

[Ulcerative Colitis]

• Characterised by relapsing, remitting episodes of inflammation that is confined to the mucosal layer of the colon
• Invariably involves the rectum and extends proximally in a continuous fashion to involve various extends of the large intestine
• Disease confined to the rectum = __________
• Disease extending to sigmoid colon= ____________
• Inflammation extending to splenic flexure = __________
• Inflammation extends proximal to the ____________ = extensive disease
• Inflammation reaches the _______= pancolitis
• Mnemonic ULCCCERS – Ulcers, Large intestine, Continuous/Colon cancer/Crypt abscesses, Extends proximally, Red diarrhoea, Sclerosing cholangitis

Answer 1

proctitis;

proctosigmoiditis;

left-sided colitis;

splenic flexure;

cecum

Question 2

[Crohn’s Disease]

• Relapsing inflammation that can affect anywhere along the entire GI tract from the mouth to the anus, most common site of involvement is the ___________
• Transmural inflammation, discontinuous – can result in strictures, perforation
• Complications – abscesses, fistulae
  = Fistulas – can be internal (_____________ joining 2 small bowel loops) or external (____________ joining small bowel to abdominal wall)

Patients with perianal Crohn’s disease are characterised by presence of __________ that can be complicated by abscess formation

Answer 2

ileocecal region;

enteroenteric fistula; enterocutaneous fistula;

perianal fistulas

Question 3

[Aetiology and pathogenesis – remains unclear]

• Thought to be due to a dysregulated immune response to luminal microbial antigens in a genetically susceptible host
  o Environmental triggers – important role in IBD too
• Increased intestinal permeability – appears to play central role in the pathogenesis of IBD
  o Intestinal epithelium acts as barrier between luminal contents and ______________
  o Complex and tightly regulated interplay between intestinal microbes and host mucosal immune system to maintain a healthy GI tract
• Defective intestinal barrier (due to damage to epithelium and leakiness of tight junctions) and _________ (due to reduced diversity, changes in gut microbiome composition)
  o Defective intestinal barrier allows bacteria-derived molecules into the mucosa – disrupted or dysregulated innate and adaptive immune response, predominantly proinflammatory cytokines
  o Leads to uncontrolled inflammation and bowel wall damage (inflammation, ulceration)
  o Decrease of the butyrate-producing species ____________ and _____________ appears to define dysbiosis in patients with IBD in Asia
• A leaky gut may be an initial event in the pathogenesis of inflammatory bowel disorders – allowing bacteria-derived molecules into the mucosa and flaring up uncontrollable inflammatory signal cascades

Answer 3

mucosal immune system;

dysbiosis;

Roseburia hominis; Faecalibacterium prausnitzii

Question 4

[Factors involved in Inflammatory bowel disease]

1. Genetic factors and IBD
   - Family history of IBD – seen in 25% Crohn’s disease patients and 20% ulcerative colitis patients

• The most compelling clinical evidence for the heritable risk of IBD has been obtained from twin studies, which also suggest that genetic factors may be more important in Crohn’s disease than in ulcerative colitis (UC)
  o In a study that included 80 twins with IBD, the concordance rate for monozygotic twins was markedly higher in Crohn’s disease than ulcerative colitis (_________ percent) and continued to rise over time
  o First-degree relatives of patients with IBD are approximately __________ times more likely to develop the disease than the general population
  § First-degree relatives of patients with Crohn’s disease have a greater increased risk of developing Crohn’s disease than ulcerative colitis – risk of developing ulcerative colitis is greater than the general population
  § First-degree relatives of ulcerative colitis patients have a greater increased risk of developing ulcerative colitis than Crohn’s disease
• More than 200 susceptibility foci has been identified so far
  o Important susceptibility foci for Crohn’s disease – NOD2/CARD 15, ATG16L1, IRGM
  o Associated with both Crohn’s disease and ulcerative colitis – IL23R
  o Different susceptibility genes in the East and West
  o IN the east – _________ no role in Asian IBD
  § Crohn’s disease – associated with _____________
  § Ulcerative colitis – TNF-308 polymorphism, ________

Answer 4

50 versus 19;

3 to 20

NOD2,ATG16L1;

ATG16L2, TNF-SF15;

CTLA-4

Question 5

[Aetiology and Pathogenesis]

2. Environmental factors and IBD – genetic factors confers susceptibility to IBD, actual disease still dependent on environmental triggers

• Environmental factors likely play a major role in the rising incidence of IBD in the East
  o Westernised lifestyle, increased consumption of refined sugar, fatty acids, fast food, reduced consumption of fruits, vegetables, fibers
• Urbanisation – better hygiene status, less microbial exposure and pollution
• ___________ – protective of IBD
• Smoking – protective of ulcerative colitis
  o West – protective of ulcerative colitis, risk factor for development of Crohn’s disease and complications.
  o East – may not be a risk factor for Crohn’s disease
• _____________ – protective of UC
• _________ – associated with exacerbation of IBD

Answer 5

Breast Feeding;

Appendectomy;

NSAIDs

Question 6

Differences of IBD in the East compared to the West
- Lower incidence and prevalence of IBD, but higher prevalence of males with CD, with different susceptibility genes
- Ulcerative colitis – appears milder, lower __________ with similar extent of disease
- Crohn’s disease – same, if not, more severe than west
o More __________ than west
o Similar disease location, behaviour and progression
o Less extra-intestinal manifestations – most commonly _________, least commonly _________________
o Less familial clustering, lower rates of dysplasia and colorectal cancer- likely to rise with rising incidence/prevalence of IBD

Answer 6

colectomy rate;

perianal disease;

arthritis; primary sclerosing cholangitis

Question 7

[Ulcerative Colitis vs Crohn’s Disease - Disease location]

Ulcerative Colitis
- Colon – with 1/3 of patients in each category
- Proctitis or proctosigmoiditis (15 to
35%)
- Left side disease (35 to 35%)
- Extensive disease, including pancolitis (45 to 50%)

CD
- Any portion of the GI tract can be involved – majority having ileocolonic disease
- 90% of patients <20 years old have _________ compared with 60%
of those >40 years old

Answer 7

small bowel involvement

Question 8

[Ulcerative Colitis vs Crohn’s Disease- Distribution of inflammation]

UC:

• Inflammation is continuous, extending proximally the __________ – rectum is almost invariably involved
• Inflammation is confined to the _____________

CD

• _________ are common, with intervening areas of normal mucosa, and the rectum is often spared
• Inflammation is transmural

Answer 8

anorectal junction; mucosa and submucosa

Skip lesions

Question 9

[Ulcerative Colitis vs Crohn’s Disease- Ulcers]

UC:

• Tend to be smaller and _______
• Large deep ulcers may be seen – poor prognostic feature

CD:
- Longitudinal and ________ with intervening areas of normal mucosa – typical _________ appearance.

[Ulcerative Colitis vs Crohn’s Disease- Terminal Ileum]

• UC: Usually not involved – unless there is _____________ (may be present in 15 to 20% of patients with pancolitis)
• CD; commonly involved

[Ulcerative Colitis vs Crohn’s Disease- strictures & post operative recurrence]

• UC: no
• CD: yes

[Ulcerative Colitis vs Crohn’s Disease- Serology]

• UC: Tend to have positive _______ and negative _______
• CD: Negative ________ and positive ______.

Answer 9

superficial;

serpiginous; cobblestone

backwash ileitis

pANCA; ASCA

pANCA; ASCA

Question 10

Symptoms and presentations of IBD – symptoms that patients present with often reflect the site of inflammation

• Colitis – often present with symptoms of per rectal bleeding, ____________, urgency and chronic diarrhoea
• Perianal Crohn’s disease – often present with anal pain, _______________ and sometimes even difficulty in passing stools as a result of the pain
• Small bowel disease – can present with abdominal pain, weight loss, tiredness and lethargy, diarrhoea and abdominal mass

Answer 10

passage of mucus;

abscess with purulent discharge

Question 11

Symptoms of Ulcerative Colitis

• Majority of patients will have ____________ –> visible blood in stools
• Passage of mucous
• Rectal urgency and tenesmus
• Chronic diarrhoea
• ________ diarrhoea – when severe enough

Answer 11

per rectal bleeding; Nocturnal

Question 12

Symptoms of Crohn’s Disease

• Often present with abdominal pain
• Ileocecal involvement – often _________ pain (sometimes mimics acute appendicitis)
• Stricturing disease can lead to lower and __________ pain – result of intermittent partial intestinal obstruction
• May present with chronic diarrhoea with visible blood in stools (lower frequency compared to ulcerative colitis)
• Weight loss is common
• Important to always enquire about __________ – may have perianal disease
• Perianal fistula (10%) – proctalgia, perianal pain, abscess

Answer 12

right lower quadrant; periumbilical; perianal pain

Question 13

Diagnosis of IBD – based on a combination of clinical, endoscopic, radiological and histological findings

[Lab features]
- Low Hb – blood loss from GI bleeding
- Elevated platelets – reactive __________
- Decreased albumin – GI loss increased
- Increased c-reactive protein, erythrocyte sedimentation rate and stool calprotectin
together with stool leukocytes (CRP, ESR)

[Endoscopic features]

UC:

• Continuous, confluent colonic inflammation beginning in rectum (above _________ – anorectal junction)
• Loss of ____________, erosions and ulcerations
• Ulcers embedded within inflamed mucosa
• Deep ulcer – poor prognostic sign

CD:

• Discontinuous inflammation and ulceration with intervening areas of normal mucosa
• Presence of strictures and perianal lesions – fissures, fistulas and inflammation

Important to exclude an infectious aetiology
o Appropriate tests including stools tests should be performed to exclude bacterial and parasitic infections – including clostridium difficile and amoebic colitis
o __________ has very similar features with Crohn’s disease – should always be excluded by performing appropriate tests

Answer 13

thrombocytosis;

dentate line; vascular pattern;

Tuberculosis

Question 14

[Treatment of IBD] 
Traditional clinical goals
- Induction of symptomatic remission
- Maintenance of clinical remission and prevention of relapse
- Restore quality of life

Treat to target recommendations on IBD
- Discrepancies observed between clinical symptoms and more objective evidence of intestinal inflammation and bowel damage – stride guidelines
o Target we should not be just clinical remission – composite endpoint of both clinical and endoscopic remission (deep remission)
o Aim – sustained and better control of GI inflammation can lead to a change in disease course and improve patient’s long term outcome and quality of life

Composite endpoint

• UC: Resolution of rectal bleeding and normalisation of bowel habit and the resolution of friability and ulceration at flexible ____________ or colonoscopy
• • CD: Resolution of abdominal pain and normalisation of bowel habit together with resolution of ulceration at endoscopy

Timeframe
Clinical remission and patient-reported outcomes should be assessed at a minimum of 3 months during active disease in both CD and UC
- If targets are not met in these time frames, therapy should be optimised or stepped up

Assessment of endoscopic remission

• UC: 3 to 6 months after initiation of therapy
• CD: _______ months after initiation of therapy

Therapeutic armamentarium in IBD – therapy is stepped up according to severity at presentation and when there’s failure or intolerance at a prior step

Answer 14

sigmoidoscopy; 6 to 9

Question 15

[Aminosalicylates (5- aminosalicylic acid) a.k.a. mesalazine]

• Anti-inflammatory medication that works topically – effective in most patients with __________ for the induction and maintenance of remission.
• Efficacy in Crohn’s disease has been called into = question although _______ may have modest efficacy
• Examples of aminosalicylates – azo-bonded sulfasalazine, delayed release formulations such as _____, controlled release formulations such as __________, combined delayed or sustained release formulations such as salofalk granules or mesavant, and topical or rectal formulations

Answer 15

ulcerative colitis; sulfasalazine; salofalk; pentasa

Question 16

Corticosteroids – patients with more severe disease or not responding to aminosalicylates Oral steroids can be used for moderate conditions, but IV steroids are used in severe cases only.

Corticosteroids such as oral _____, prednisolone or intravenous ________ can be used to induce remission. Not good maintenance agents – many side effects from long term steroid therapy

Immunomodulators such as azathioprine/6 mercaptopurine or methotrexate can be used to maintain a steroid induced remission While ________are effective steroid-sparing maintenance agents for ulcerative colitis and Crohn’s disease, __________ is only efficacious in Crohn’s disease

Answer 16

budesonide; hydrocortisone

thiopurines; methotrexate

Question 17

Biologic therapy – patient with even more severe disease, or are not responding or intolerant to corticosteroids and immunomodulators. Can be use alone or in combination with an immunomodulator.

Anti-TNF antibody – infliximab and _________
Anti-integrin antibody – __________
Anti-IL12/23 receptor antibody – __________
JAK inhibitors – tofacitinib

Answer 17

adalimumab.;

vedolizumab

ustekinumab

Question 18

Lastly, _________ can be considered as in induction therapy in patients with steroid refractory acute severe ulcerative colitis. Patients who respond are then bridged to maintenance therapy with a thiopurine

Answer 18

intravenous cyclosporin

Question 19

Conventional treatment strategy – sequential, step-up therapy
- Treatment is usually started with the less potent but safer ___________ – more potent therapies are then added when there is lack of response, toxicity or intolerance
- Biologics are usually indicated when patient has steroid dependent or refractory disease, or have failed or intolerant to ________________
- May not be a good strategy – may result in delays of
receiving more potent and effective therapies, especially for patients with more severe or aggressive disease

Changes in IBD treatment paradigm
- Shift in treatment strategy from conventional step up approach to accelerated step up approach or even an early top down approach in patients with more aggressive disease
o Accelerated step up approach – immunomodulators are introduced earlier rather than waiting for steroid dependency
o Top down approach – patients at high risk for disease progression and complications are started earlier on biologics alone or in combination with an immunomodulators

Answer 19

5-aminosalicylic acids; immunomodulators

Question 20

[Extraintestinal manifestations of inflammatory bowel disease]
- The more commonly affected organs are the eye, joints and skin – extraintestinal manifestations may be related to bowel disease activity or can run an independent course (not affected by bowel disease activity)

Related to bowel activity

• Eye – _________
• Skin or mucous membrane – _________ (mouth), pyoderma gangrenosum, erythema nodosum
• Bone – ______________ arthritis (most common at knee)

Independent course

• Eye – uveitis
• Bone – ______________ arthritis and axial spondylitis and sacroileitis
• Liver – primary sclerosing cholangitis and autoimmune hepatitis

Answer 20

episcleritis; aphthoid ulcers; type 1 pauciarticular peripheral;

type 2 polyarticular peripheral;

Question 21

Extraintestinal manifestations of IBD – bone
- Types of peripheral arthritis
o Pauciarticular – less than _________ , asymmetrical, lower limbs more affected, self-limited for less than 10 weeks, associated with disease activity
o Polyarticular – 5 or more joints, most commonly affecting ____________ (e.g. metacarpophalangeal), symmetrical or asymmetrical, episodes of exacerbation and remission may last from months to years and not related to IBD disease activity
- Patients with spondylitis and/or sacroiliitis usually report symptoms with characteristic features of ____________, which should alert the gastroenterologist or internist to the possibility of seronegative spondyloarthropathy (SpA)
- Patients typically complain of prolonged stiffness in the back and/or buttocks in the morning or after rest – stiffness and associated pain are often relieved by exercise
o Back symptoms are generally unrelated to the activity of the IBD.
- _______ is found in 50 to 75 percent of the patients with IBD-associated axial arthritis
o An increase in frequency in HLA-B27, B35, and DRB1*0103 has been described in those with a type I peripheral arthritis
o Type II arthropathy has been associated with ________ (and not B27)

Answer 21

5 to 6 joints;

small joints;

inflammatory back pain;

HLA-B27;

HLA B44

Question 22

Primary sclerosing cholangitis – chronic, cholestatic liver disease characterized by inflammation and fibrosis of both the intrahepatic and extrahepatic bile ducts leading to the formation of ______________
- Characterised histologically by ______________
- Likely an immune mediated, progressive disorder that
eventually develops into cirrhosis, portal hypertension and hepatic decompensation in the majority of patient
- 80% of patients with established PSC will have IBD, with the majority having ulcerative colitis than Crohn’s disease
o Prevalence is lower in the east, with only approximately 20 to 50% of patients with established PSC having IBD
- Prevalence of PSC in patients with established IBD is up to about 3 to 5%
o In the east, the prevalence is lower – 0.4 to 3.1% in ulcerative colitis patients
- IBD in patients with PSC tends to have right sided disease and run a milder course
o Increased risk of developing pouchitis in those who have an _____________ and an increased risk of developing colon cancer

• Patients with PSC are often asymptomatic – should be suspected in IBD pts who develop a cholestatic LFT (liver function test)
  o With an elevation in ALP (alkaline phosphatase), GGT (gamma-glutamyl transferase) – mild elevations of ALT (alanine aminotransferase) may also been seen
  –> ALP: Elevated in ____________, excessive bone formation
  –> GGT Elevated in ___________, usually the first enzyme to rise in bile duct obstruction
  –> ALT Elevated in liver damage
  o If they develop symptoms, __________ is the most common
• Pruritus (severe itching of the skin) may become a dominant symptom if patients develop biliary obstruction
• Late symptoms include jaundice, ascites and variceal bleeding (reflecting progression to decompensated liver cirrhosis)
• MRI of the biliary tree is the modality of choice to make a diagnosis of PSC with the demonstration of the characteristic ________ appearance of the biliary tree
  o Liver biopsy is not necessary unless the biliary tree is
  normal and small duct PSC is suspected
  o Important to exclude secondary causes of sclerosing cholangitis such as HIV and _____

Answer 22

multifocal bile duct strictures;

periductal concentric onion skin fibrosis;

ileal pouch anal anastomosis;

bile duct obstruction; liver damage

fatigue;

beaded;

IgG4 cholangiopathy

Question 23

Extraintestinal manifestations related to malabsorption in Crohn’s disease – formation of gallstones and renal stones.
- In patients with ileal disease and/or ileal resection, ____________ of bile acids is disrupted, leading to GI loss of bile salts
o Depletion of bile salts leads to a more lithogenic bile, encouraging the formation of gallstones

• Crohn’s disease patients with extensive small bowel disease may have fat malabsorption – free fatty acid binds to calcium, increase in amount of ________________ in the colon (usually bound to calcium and not absorbed)
  o Also, increased colonic permeability to small molecules such as oxalate induced by exposure of the colon to non-absorbed bile salts
  o Unbound oxalates absorbed from colon and subsequently excreted in the urine – enteric hyperoxaluria
  o Oxalates in the urine then binds to urinary Ca2+ forming calcium oxalate stones
• Patients with malabsorption may have additional factors predisposing to stone formation
  o Diarrheal fluid losses can lead both to a reduction in urine volume
  o If patient has metabolic acidosis – leads to low urine pH and marked decrease in __________ excretion, promoting uric acid stones as well

Answer 23

enterohepatic circulation;

unbound oxalates;

citrate

Question 24

[Complications of inflammatory bowel disease]

Ulcerative colitis:

• Severe gastrointestinal bleeding that may be life threatening
• Development of ___________ if there is an acute severe exacerbation of – when colon dilates to more than 6cm associated with systemic toxicity such as fever, and tachycardia
• Perforation of the bowel may rarely occur as a consequence of toxic megacolon – can be life threatening.

Crohn’s disease
- Common acute complications include __________ from strictures usually located in the small bowel, microperforation with localised peritonitis or even intraabdominal abscess and perianal abscesses in patients with peri-anal disease/fistula

For both
- Increased risk of venous thromboembolism especially when they are hospitalised for acute exacerbation of disease
o These patients should receive prophylaxis with ___________________
- Iron deficiency anaemia is a common complication for IBD patients with active disease due to GI blood loss and nutritional deficiencies (treated with iron supplements)
- IBD patients are also at increased risk of metabolic bone disease due to disease related inflammatory activity, glucocorticoid therapy and nutritional deficiencies (especially for Crohn’s disease)
o ___________ should be performed in IBD patients who had more than 3 months of corticosteroid therapy, has poor nutrition and low body weight, had previous fragility fractures and in postmenopausal women and in males >50 years old
o Treatment – weight bearing exercises, avoidance of smoking/alcohol, supplementation of calcium/vitamin D, bisphosphonates

Answer 24

toxic megacolon;

small bowel obstruction;

low molecular weight heparin;

Bone densitometry

Question 25

Colorectal cancer
- Patients with long standing ulcerative colitis and Crohn’s colitis are at increased risk of developing colorectal cancer
o Risk increases with duration of disease and starts at 7 years from the time of diagnosis and increases linearly thereafter
o Recent time trends suggest that there is a trend for lower risk for CRC in recent years

• Other risk factors –
  o Extent of disease – patients with extensive disease have a higher risk compared to those with ____________, who has an intermediate risk
  o Crohn’s patients with >1 segment of colon involvement – increased risk
  o Ulcerative colitis patients with disease limited to the rectum i.e. proctitis – risk similar to the general population
• Severe inflammation, family history of colon cancer and PSC all increases the risk of colon cancer
  o Ulcerative colitis patients with PSC has a 3 fold higher risk of developing colon cancer compared to those without PSC
  o Screening colonoscopy should be performed beginning at 8 years after the onset of symptoms, and at the time of diagnosis of IBD-PSC

Answer 25

left sided disease

Question 26

[Surgery for inflammatory bowel disease]
- Surgery is an important component of the therapeutic armamentarium for IBD

Considerations for surgery
Ulcerative colitis 
- Medically refractory disease
- Dysplasia and cancer
- Life threatening acute complications – severe bleeding, toxic megacolon and \_\_\_\_\_\_\_\_

Crohn’s disease
- Medically refractory disease
- Complications – perforation, abscesses, fistulas, symptomatic strictures with intestinal obstruction
- Significant GI bleeding that cannot be arrested via endoscopic or radiological means
- Cancer
Procedures

UC
- Total colectomy with Ileal pouch anal anastomosis
(IPAA)
- End ______

CD:

• Depend on disease and location
• __________ or resection for small bowel strictures, Segmental colectomy for Crohn’s colitis

Answer 26

perforation;

ileostomy;

Strictuloplasty