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Delta Med - Gastroenterology > Gastroenterology 2 - IBD > Flashcards

Gastroenterology 2 - IBD Flashcards

1
Q

What are elements of the montreal classification for CD/UC?

A

Age, CD location, CD features (perforating/stenosing), UC - proctitis, left sided or extensive

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2
Q

What are the predominant cytokines involved in the pathogenesis of IBD?

A

TNF-a, IL-1, 6, 8, 12, 17, 23, IFN-gamma

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3
Q

What is the familial pattern of inheritance in IBD?

A

Familial incidence 10-15%
Monozygotic concordance > dizygotic
CD 44-58%, UC 6-18%

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4
Q

What are significant genes implicated in the pathology of CD?

A

NOD2
PTPN22
ATG16L1
IL23R

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5
Q

What are signifcant genes implicated in the pathology of UC?

A

ECM1
CDH1
LAMB1

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6
Q

What are genes implicated in both UC and CD?

A 
Il23R
MST1
IL10
CARD9
DRB*103
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7
Q

What is the pathogenesis of NOD2/CARD15 mutations in CD?

A

Increases risk - up to 40% are carriers in CD pop vs 16% normals.
IBD1 gene encodes NOD2
deficient activation of NFkappa-beta in recognition of baterial peptidoglycan fragments

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8
Q

What is the relationship between NOD2 and surgery?

A

Significantly reduces the chance of survival from surgery in patients with NOD2/CARD mutations.
(Ileal CD)

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9
Q

What are important environmental factors in IBD?

A

Smoking increases risk of CD by 90%, with increased risk in ex-smokers. Refractory/fistulising disease/recurrence

Appears to be possible linke with E.coli, measles, para TB.

Faecalibacterium prausnitzii may be protective

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10
Q

What is the natural history of crohn’s disease?

A

Natural progression from inflammatory, to stricturing to penetrating disease with time

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11
Q

What proportion of CD patients require surgery?

A

75% of CD patients will require at least 1 resection, and 50% of those patients will have a clinical relapse.

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12
Q

What is the extent of CD at diagnosis?

A

Approx 1/3 pancolitis, left sided and proctitis respectively.
1/3 of limited disease extends at 10yrs
50% relapse in the 1st year post Dx
1/4 are in remission 5 years post Dx, 18% have continuous activity and 57% have intermittent relapses
only 50% of patients are in remission at any given time.
Up to 44% of pancolitis patients require colectomy at 5 years, 10% rectosigmoid disease.

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13
Q

What are key ages wrt CRC risk in UC?

A

risk begins to increase at 10 years, and peaks at 30 years.
Increase disease extent leads to increased risk of CRC.
6% lifetime risk in UC, double controls

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14
Q

What is the relationship between PSC, UC and CRC?

A

risk of CRC is high, and can occur early.
33% at 20 years of disease - start screening at diagnosis, annual surveillance, and consider prophylactic URSO or surgery

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15
Q

What is the relationship between FHx and CRC?

A

Patients with CRC FHx and IBD have significantly higher risks of CRC - 29% in patients with CRC in 1st degree relative

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16
Q

What is the relationship between cancer risk in UC and disease activity?

A

OR 2.54 if macroscopic inflammation

OR 5.13 if histological inflammation

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17
Q

What are guidelines for IBD surveillance?

A

use HD scopes with chromoendoscopy.
If polyploid or non-polyploid dysplasitc lesions are completely removed, endoscopic surveillance can be performed instead of colectomy.

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18
Q

How often should CRC surveillance be performed in CRC?

A

Annually in active disease, PSC, FHx in 1st degree relative, colonic stricture or multiple pseudopolyps, previous dysplasia.

Q3Y in inactive UC, Crohn’s colitis, IBD and FHx in 1st deg relative >50

Q5Y in patients with two normal colonoscopies

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19
Q

What are predictors of severe crohn’s disease?

A

Perianal disease
Need for steroids
Fibrostenosing disease
Loss of weight >5kg (loss of weight and strictures do worst)

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20
Q

What features at Dx predict severe CD?

A

Steroids at Dx OR 3.1

Age

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21
Q

What are serological markers in IBD?

A

ASCA and pANCA can differentiate between CD and UC:

pANCA + in 70% UC
ASCA + in 40% Crohn’s

pANCA + and ASCA - is 90% PPV for UC
ASCA + and pANCA - is 95% PPV for CD

Can use CRP and calprotectin to identify patients with IBD in need of further Ix

ASCA, Anti OMPC, CBir1 (flagellin) predict more severe disease in CD

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22
Q

What are aims of IBD therapy?

A

Treat to target - control disease, not just symptoms
- mucosal healing, normal CRP, calprotectin, imaging improvement

Maintain QoL
Prevent disease related complications
Avoid therapy related complications

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23
Q

What are features of high risk CD?

A

age

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24
Q

What are features of high risk UC?

A

Age

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25
Q

What are principles of UC treatment?

A

UC disease severity generally related to symptoms.
Treat UC according to extent and severity.
5-ASAs oral and rectal
Steroids if inadequate control with 5-ASA, always taper (40mg for 1-2 weeks, then taper 10mg/week to 20, then 5mg/week thereafter)
Thiopurines if needing steroids greater than 1xyear
Anti-TNFs
Vedolizumab
consider MTX, CYC/Tacro

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26
Q

What is the approach to management of CD?

A 
Disease activity =/= symptoms
Rapidly step up therapy if:
 - active disease
 - extensive disease
 - complicated disease - fistula = TNF
 - not reaching target
Stop smoking!
Early introduction of effecive Rx is more effective (time is gut)
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27
Q

What is the relationship between CRP and outcomes in IBD?

A

worse outcomes with high CRP levels - related to disease extent at Dx in UC, but not CD.

3x rate of surgery w CRP >10 at 1 year in UC
2x rate of surgery w CRP >10 at 1 year in CD

28
Q

What is the relationship between steroid free remission and CRP normalisation?

A

Significantly higher rates of remission achieved withouts steroids i patients who achieved complete normalisation or significant decreases in CRP with therapy.

29
Q

What is the role of fecal calprotectin in IBD?

A

Fecal calprotectin is an accurate method of determining active disease and remission in IBD and predicts risk of IBD relapse.

30
Q

What is the relationship between mucosal healing and prognosis in UC and IBD

A

Predictors of MH in UC - education more than 12 years and extensive disease. Reduced colectomy rate was noted in patients who had achieved mucosal healing at 1 year.

In CD, predictors of MH included fever at diagnosis and treatment without steroids.
Reduced endoscopic activity and reduced steroid use were noted in CD who had achieved MH at 1 year.

31
Q

What are features of mucosal healing and a top down treatment approach?

A

Increased rates of mucosal healing at 2 years with top down approach and 3/4 steroid free at 4 years.

32
Q

What is the relationship between deep remission and outcomes?

A

Increased quality of life in patients who achieve deep remission with treatment

33
Q

What is the role of endoscopic therapy in IBD?

A

increased frequency of endoscopic assessment with subsequent treatment alteration leads to increases in rates of mucosal healing.

34
Q

What is the efficacy of Melsalazine in UC?

A

Effective in achieving partial and complete response in 50% and 24% of patients at dose of 4.8g/day

Higher rates of cessation of bleeding were achieved in rectal and oral vs either route alone.

Low dose may be chemoprotective in UC and CRC

35
Q

What are common toxicities in 5-ASA?

A 
Interstitial nephritis
Pancreatitis
Blood dyscrasias
Diarrhoea
Secretory diarrhoea

Unique to salazopyrin - sulfur intolerance, SJS, Azoospermia (not in other non-sulfur compounds)

Potential AZA-6MP interaction (mild only)

36
Q

What is the role of 5-ASA in Crohn’s disease?

A

Likely none - probably doesnt work.

May have a role in mild colinic crohn’s or post ileal resection - likely non clinically significant benefits.

37
Q

What is the role of antibiotics in Crohn’s?

A

probably don’t work in non-fistularising crohn’s disease.
May help in augmenting steroids (cipro and flagyl) in achieving remission at 8 weeks.
Help heal post op crohn’s (nitromidazoles)

38
Q

What is the role of steroids in IBD?

A

Effective at achieving remission in UC and CD, 30% heal mucosa.

NOT for maintenance, induction agent only. Non-durable long-term outcomes

Give 40mg/day for 7-28 days (a/w clinical response), then taper 10mg/week for 2 weeks, to 20mg, then 2.5-5mg/week

Budesonide is favoured in ileocolonic CD, but not available in australia.

39
Q

What are significant steroid AEs in CD?

A

55% IBD patients have ADs
- cushingoid, weight gain, bruising, neuropsychiatric effects, osteopenia/fractures
DM, HTN, glaucoma

Lead to excess mortality, and excess infections (above infliximab or other immunomodulators)

40
Q

What is the role of AZA in CD and UC?

A

CD: Effective in steroid sparing (NNT = 3), maintenance of remission (NNT = 6)

Effective in maintenance of remission in UC!

Also reduces hospitalisation and surgery in CD and UC

41
Q

What is the role of early immunomodulatory therapy in CD?

A

May decrease the risk of requiring CD surgery

42
Q

What is the rationale for monitoring AZA therapy?

A

TPMT converts 6-MP to 6-MMP (inactive) and 6-MMPR (hepatotoxic). Also converted to 6-TGN by HPRT, IMPDH and GMPS to 6-TGN (Rac-1 blockade, T-cell apoptosis: active metabolite)

Metabolite testing is most useful in patients not responding or experiencing AEs to thiopurines

43
Q

What is the role of adding allopurinol to AZA therapy?

A

used to block TPMT in shunters, and increase levels of active metabolite along with reduction of original AZA dose.

44
Q

What are primary AEs associated with AZA?

A 
Myelosuppression
Hepatitis
Pancreatitis
N/V/Flu-like/Hypersensitivity syndrome
Infection
Lymphoma

Minimise with regular blood tests, pre Rx TPMT activity, drug level monitoring (mercaptopurine slightly better tolerated)

45
Q

What were the outcomes of the CESAME cohort study?

A

Higher rates of lymphoma and non-melanoma skin cancer during thiopurine and post thiopurine use.

46
Q

What is the utility of MTX in CD and UC?

A

MTX is effective maintenance therapy for remission and induction in CD, but not in UC

METEOR trial showed that MTX was not superior to placebo in inducing remission in CS dependent UC

47
Q

What are 2 anti-TNF medications approved on the PBS for CD?

A

infliximab and adalimumab are approved for inflammatory CD and fistulizing CD refratory to steroids, AZA/6MP/MTX with a CDAI >300. Must demonstrate response CDAI

48
Q

What are benefits of infliximab in inflammatory CD?

A

Improved rates of clinical response, clinical remission, reduced hospitalisation, surgery and increased mucosal healing.

Higher rates with Adalimumab 40mg weekly

Remission is retained in these patients.

49
Q

What are risks associated with TNF therapy in CD?

A 
Infection -TB, invasive fungal, viral infections (Bact sepsis rare)
Lymphoma ?inc with TNF monotherapy
Demyelinating disorders
Drug induced lupus
CHF
Hepatic abn
Dermatologic-psoriaform reactions
50
Q

What medications are associated with increased serious infections and mortality in the TREAT registry?

A

corticosteroids and narcotic analgesics increased rates of infections and mortality, whereas IFX, 6-MP, AZA, MTX did not.

Increased lymphoma risk is driven by 6-MP, not by anti-TNF (HSTCL)

51
Q

What is the evidence supporting the use of adalimumab/infliximab in UC?

A

higher rates of clinical response vs placebo in infliximab (ACT study)

Adalimumab has higher proportion of mayo remission score in ADA arm, and reduced hospitalisations (all cause and UC-related)

52
Q

What is the MoA of vedolizumab and it’s use in IBD?

A

Vedolizumab = anti alpha4/beta 7 integrin - efficacious and safe in UC (better than placebo as induction and maintenance therapy in mod-severe acute UC)

effective in clinical remission in CD patients, in all except anti-TNF failures at 6 weeks.

53
Q

What are advantages in top down therapy vs step up therapy?

A

Shows higher rates of patient achieving remision at week 4, 6 and 12 months, in addition to higher rates of mucosal healing at 2 years

54
Q

what is the benefit of combination IM and anti-TNF therapy?

A

improved efficacy
however increased opportunitstic infections and increased risk of hepatosplenic T-cell lymphoma

better rates of steroid free remission and mucosal healing in UC patients

55
Q

What are issues with immunogenicity with infliximab?

A

antibodies form in 15-60% of patients
associated with loss of response, reduced drug levels and infusion reactions.
can prevent with q8w infusions, steroid premedication and immunomodulators

56
Q

What is the rate of relapse following cessation of AZA in CD?

A

48.5% overall relapse rate.

Also 44% relapse rate at 1 year in patients with IFX withdrawal, however successful re-treatment in 88% (STORI)

Predictors of relapse:
Hb 6, RCP >5, CDEIS >0.

(patients not in deep remission relapsed)

57
Q

What is the management of acute severe ulcerative colitis?

A

Initially IV hydrocortisone 100mg QID, clexane, IV fluids and transfuse to Hb >100.

Perform AXR (45 or BM >8 - 85% require colectomy

If clinical response, continue

If none at day 5, either salvage therapy or surgery

58
Q

What are options for salvage/surgery in UC?

A

Cyclosporine/Infliximab OR J-pouch, total colectomy

59
Q

What were outcomes of the CYSIF trial?

A

Found that response rate at day 7 in severe acute ulcerative colitis was equal in both IFX and Cyclosporin groups.

Local data more recently seems to favour Inflixmab over cyclosporine - lower rates of colectomy in IFX group and better in long term.

60
Q

What are issues with pouch surgery?

A 
Mortality 1%
Pouchitis 50%
SBO 18%
Fistulae 7%
Reduced fertility
61
Q

What are features of pouchitis?

A

Affects 50% of patients receiving a pouch.
Recurrent/chronic pouchitis affects 10-15%
Can use Cipro/MTZ and probiotics
Predictors: PSC, high pANCA, non-smoking, females, NOD2

62
Q

What are features of fistulsing crohn’s disease?

A 
20-50% in CD
median time to heal 2.6 years
Relapse in 30-50%
No associated with ileal penetrating disease
proctectomy required in 20-25%
63
Q

What is the management of fistula in CD?

A

EUA/MRI/EUS
If superficial - Ab, consider Fistulotomy, observe
If complex: seton + Ab + Anti-TNF +/- IM
Evaluate with MRI on anti-TNF
if failure Tacrolimus, if failure definitive surgery.

64
Q

What are evidence based medical management measures in fistulas in CD?

A

ciprofloxacin has been shown to be of benefit when combined with anti-TNF
infliximab - ACCENT II has highest level of supporting data

65
Q

What were outcomes of the POCER study in post-op CD?

A

Treatment according to risk, based upon endoscopic findings at 6 month, is superior to drug therapy alone. Step up with anti TNF thearapy based on colonoscopy in high risk patients.

(thiopurine/anti-TNF in high risk patients)

66
Q

What combination therapy has the highest risk of opportunitstic infections in IBD?

A

AZA/6MP + corticosteroids has P value of 17.5

Should vaccinate for
Hep b
HPV + pap smears
VZV (live attenuated - 3 weeks pre anti-TNF/IM)
Pneumococcal polysaccharide vaccine
Influenza trivalent inactivated vaccine

Delta Med - Gastroenterology (3 decks)

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