Transcript Case presentation

Inflammatory Bowel
Disease
Kevin Luey, FRACP
Gastroenterologist
Inflammatory Bowel Diseases
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Infective colitis
Ulcerative colitis
Crohn’s colitis
Ischaemic colitis
NSAID-colitis
Radiation colitis
ULCERATIVE COLITIS
CROHN’S DISEASE
IBD
Chronic inflammatory disorders of
the gastrointestinal tract of
unknown aetiology but with an
autoimmune basis, characterised
by ulceration and inflammation of
the gut wall, causing abdominal
pain, diarrhoea and rectal
bleeding.
Prevalence
Prevalence varies world wide being more common in
developed countries. 100-200 per 100,000 in
western countries. ? Underestimate.
Higher prevalence in white races and Jews.
More common in close relatives.
The prevalence of Crohn’s in the NZ population is
approximately 100 per 100,000
Incidence
Was doubling every 10 years since 1940
Improved recognition
Appears to be increasing slowly now.
Real increase
Currently 10-20/100,000
Pathogenesis
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Still unknown nearly 100 years after first
description
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A combination of environmental factors
triggering chronic inflammation in a genetically
predisposed hosts.
Pathogenesis of IBD
genes
microflora
food
smoking
drugs
mucosal immunity
mucosal inflammation
IBD
Differences between Crohn’s and
UC
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Differences in disease phenotype
Differences in genetic associations (e.g. IBD1 on
chromosome 16 coding for NOD2 important in
CD but not UC)
Both diseases long thought of as centering on
upregulated immune reactivity, but
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increasing evidence of disordered innate immunity in
CD
Phenotype Differences between
Crohn’s disease and UC
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Crohn’s Disease
Transmural
Small and large bowel
Skip lesions
Rectal Sparing
Granulomata common
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Ulcerative Colitis
Mucosal
Large bowel only
Continuous disease
Rectal involvement 95%
Granulomata uncommon
Clinical presentations
and patterns of disease
IBD: key clinical factors.
Presentation
Natural History
diarrhoea, often bloody Onset any age, peaks early
adulthood and 40-60
abdominal pain
Relapse and remissions
weight loss
life-long
malaise
Ulcerative colitis
Clinical features
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Unformed stools
Blood and mucus
Abdominal cramps
Urgency
Tenesmus
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Disease distribution
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Begins in rectum and extends
continuously proximally
UC Clinical course
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Natural history
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Fulminant (often first
episode)
Chronic relapsing and
remitting
Chronic continuous
Self limiting (<10%)
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Relapse rate
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50% in first year
Colectomy
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Pancolitis 30-40% in 5 yrs
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Distal colitis; 10% in 5 yrs
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1%/year thereafter for all
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These rates appear to be falling
since Infliximab has become
available
ASSESSING SEVERITY OF UC
(Truelove & Witts BMJ 1954)
mild
stools
<5/d, trace blood
temperature No fever
pulse
severe
>5/d, bloody
>37.8
<90
>90
Hb
Normal
<10.5
ESR
<30
>30
Crohn’s disease
Clinical features
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Systemic symptoms
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Due to chronic
inflammation
Lethargy
Loss of appetite
Weight loss
Fever
Intestinal symptoms
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Depend on disease
distribution
Abdominal pain
Diarrhoea
Weight loss
Rectal bleeding
Nausea
Crohn’s disease
Sites of involvement
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Small bowel
30%
Terminal ileum
80%
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Small and large bowel
50%
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Large bowel
20%
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Diagnostic
investigations
Diagnosis
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Stool culture
Blood tests
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Endoscopy and histology
Radiology
Nuclear med scans
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Inflammatory markers
Nutritional markers
White cell scans
DEXA
ASCA/ANCA
Faecal calprotectin
Blood tests
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Raised CRP/ESR
Raised platelets: correlate well with IBD rather
than infectious colitis
Hypoalbuminaemia: correlates with high CRP
Full blood count – anaemia, neutrophilia
Iron, Vitamin B12, folate
Renal function
Liver function
Endoscopy
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Oesophogastroduodenoscopy (gastroscopy)
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Ileo-colonoscopy (colonoscopy)
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Enteroscopy (small bowel)
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Capsule endoscopy
Endoscopy (ILEO-colonoscopy)
Histology
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Crypt distortion (implies inflammation for more
than 6 weeks)
Chronic inflammatory cells
Granuloma formation
Can help with diagnosing microscopic colitis
Radiology
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Plain films
Contrast studies ? outdated
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CT
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Collections (e.g. abcesses)
Complications
US
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Ba follow through, enema
Bowel wall thickening
Collections
MRI
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Perianal disease
Small bowel
AXR IN ACUTE UC
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Transverse colon
dilation, mucosal
islands and thumbprinting
Crohn’s disease
Ileal stricture: CT enteroclysis
Ileal stricture: MRI
Treatment strategies
MANAGEMENT OF IBD
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General
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Education - CCSG
Psychological support
Nutritional support
Avoid risk factors
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smoking, drugs
‘MDT’
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GP, physician, surgeon,
counsellor, nurse,
pharmacist, dietitian
Specific therapy
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medical, surgical
Ulcerative colitis
Ulcerative colitis
goals of therapy
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Induce remission
Maintain remission
Quality of life (IBDQ)
Prevent complications
Disease
 Therapy related
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Appropriate timing for surgery
Ulcerative colitis
Therapeutic considerations
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Extent
Severity
Disease complications
Response to previous therapies
Lifestyle considerations
UC Treatment Options
5 ASA – topical / oral
 Steroids – topical / oral / systemic
 Azathioprine/6-MP/Methotrexate
 Cyclosporine – oral / systemic
 Immunological therapies - biologics
 Surgery
 Alternative therapies – e.g. Probiotics
No treatment entirely effective or safe
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Management of fulminant colitis
mortality reduced from 50% - 1.5%
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Meticulous clinical care
Multidisciplinary approach
IV hydrocortisone 100mg qds (60%)
Prophylaxis against DVT/PE
Cyclosporin 2mg/kg (levels 150-250)
60% initial response, 30% long term
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? Biologics
Azathioprine on discharge
5 ASA for active UC
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60% remission
OR 2.0 cf placebo in metaanalysis
Topical in left sided disease
(70% response)
Dose dependant
Renal toxicity
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Dose dependant nephritis
Class effect
Which 5ASA? What dose
stomach jejunum ileum colon
Pentasa
(slow-release mesal)
Asacol, Salofalk
(pH-dependent mesalazine)
sulphasalazine, olsalazine, balsalazide
(azo-bonded)
CORTICOSTEROIDS IN IBD
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Restrict to active IBD
No prophylactic role
Co-prescribe bone protection
Minimise long-term use
RESPONSE TO STEROIDS IN IBD
65% remission/improvement in 4/12
50% Crohn’s patients relapse or are steroiddependent at 1 year
`
PROBLEMS WITH STEROIDS
Given inappropriately
Recurrence after stopping
Side-effects
Failure to heal mucosa
SIDE-EFFECTS OF STEROIDS
osteoporosis - give calcium/vit D
diabetes
infections
osteonecrosis of hip
hypertension
glaucoma/cataracts
skin changes……….
Maintenance therapy for UC
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5 ASA
Azathioprine
Biologics
Azathioprine
Long term maintenance strategy
 Slow onset 2-3 months
 Mainly uncontrolled data
 36% 1 year relapse compared to 59%
??duration of therapy
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Side effects of Azathioprine
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Allergic responses
Leucopenia
Nausea and vomiting
Pancreatitis
Dermatological
? Malignancy
? Effects in pregnancy
Monitoring: regular FBC and LFT
Surgery for UC
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Fulminant colitis
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Failed medical treatment
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Complications
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Cancer risk
Surgery for UC
Panproctocolectomy
Ileostomy
Pouch formation
Close stoma
Crohn’s disease
Crohn’s disease
Goals of therapy
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Similar to UC
Nutrition/growth
Surgery – Not curative
- High relapse rate
Fistula management
5ASA INDICATIONS
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Crohn’s
mild-moderately active disease – esp. colon
 ? Effectiveness as maintenance
 prophylaxis only after small bowel resection
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Steroids in Crohn’s disease
Gut, 1994; 35: 360
Antibiotics in Crohn’s disease
Metronidazole
Perianal / colonic disease
?active disease
Some benefit post surgery 1yr
Neuropathy
Azathioprine as maintenance in
Crohn’s disease
Benefit at 2.5mg/kg but not much beyond
Methotrexate in Crohn’s disease
Start 25mg s/c weekly MTX for 16 weeks
Then maintain with 15mg s/c or oral weekly
Side effects of methotrexate
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Allergic reaction
Folate deficiency
Oral ulceration
Bone marrow suppression
Pneumonitis/pulmonary fibrosis
Hepatic fibrosis
Teratogenic
Healing of Colonic Ulceration with
Anti-TNF Antibodies
Van Dullemen Gastroenterology 1995
Biologics
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Anti- TNF alpha antibodies.
TNF alpha important near the beginning of the
inflammatory cascade
Blocking this prevents inflammation and
resultant ulceration etc.
Anti-TNF Antibodies
Binding Site for TNF
IgG
•Infliximab
•Chimeric monoclonal antibody
•Given as iv infusions (approx every 2 months)
•Adalimumab
•Fully humanised
•Given as subcut injection every 2 weeks
k
k
Infliximab Results
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Chronic active
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30% remission
30% improvement
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Fistulation
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Early recurrence on stopping
Concurrent immunosuppressives or
maintenance therapy essential
60% closure
General Contraindications
Intestinal sepsis
 pregnancy, lactation (experience reassuring)
 Infection – check esp. for TB
 heart failure
 malignancy
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Side Effects
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infusion reactions
acute 20%
 delayed hypersensitivity 2%
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ANA - 50% dsDNA Abs
lymphoma?
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aplastic anaemia
heart failure
demyelination,
aseptic meningitis
infections
!!Cost - $5000 per infusion!!
Adalimumab
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Humanised alpha TNF antibody
Therefore less immunogenic
Given subcutaneously rather than iv
Similar results to Infliximab
Same precautions and side effects
Given 2 weekly
COMPLICATIONS OF IBD
LOCAL
 ulceration
 bleeding
 stricture
 perforation
 fistula
 abscess
 cancer
SYSTEMIC
 eyes
 joints
 skin
 liver
 thrombosis
Extra-intestinal manifestations of
IBD
Erythema
nodosum
Pyoderma
gangrenosum
Colorectal Cancer in UC
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High risk in Ulcerative Colitis
Very high risk if have sclerosing cholangitis
Risk increases with duration and extent of
disease
2% after 10 years
 9% after 20 years
 19% after 30 years
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Colonoscopic Surveillance in UC
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Recommended colonoscopic surveillance with
multiple biopsies
Every 2 years from 8-10 years after diagnosis
 Annually after 20 years
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High grade dysplasia – colectomy
Low grade dysplasia ? Colectomy
? 6 monthly colonoscopies
Colorectal Cancer in Crohn’s
Colitis
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Evidence less clear cut than in UC
Increasing evidence that the risk is similar to UC
in Crohn’s colitis.
Most experts recommend same surveillance
programme as for UC
PROGNOSIS OF IBD
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lifelong relapses and remissions
bowel resections
»
»
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UC 20%
Crohn’s 70%
mortality increasing slightly in Crohn’s
mortality decreasing rapidly in UC
Time trends of death from ulcerative colitis (full line) and Crohn's disease (dashed lines).
Sonnenberg A Int. J. Epidemiol. 2007;36:890-899
Published by Oxford University Press on behalf of the International Epidemiological Association ©
The Author 2007; all rights reserved.
Summary
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IBD common and affects wide range of age groups,
often the young
Multidisciplinary and holistic care is essential in such a
chronic condition
Treatment relies on induction of remission then
maintenance with anti-inflammatory and
immunosuppressive treatments
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Steroids are not useful for maintenance
Immunosuppressive regimens are applied in a step-wise
approach
UNDERWRITERS’ VIEW
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INCREASING PREVALENCE
DECREASING MORTALITY – Life ratings
MORE EFFECTIVE MEDICATIONS but
not without morbidity – probably balancing out
for TRB and Trauma (critical illness) ? For IP
BOWEL CANCER RISK LOWER THAN
PREVIOUSLY THOUGHT – Trauma and IP
Future genetic tests ?