Inflammatory Bowel Disease Flashcards
What investigations are done for ulcerative colitis?
Chronic, relapsing, remitting inflammation of the GI tract
What are examples of inflammatory bowel disease?
Crohn’s disease
Ulcerative colitis
What do Crohn’s disease and ulcerative colitis differ in?
Location and inflammation
When does inflammatory bowel disease commonly present?
In the teens and twenties
how many people have IBD in the UK?
620,000
What can IBD be due to?
Genome
Microbiome
Environment
Is IBD medelian inherited?
No, but has genetic susceptibility
IBDU
There are 2 forms- collagenous colitis (thickening of subepithelial collagen band) and lymphocytic (increased no of lymphocytes) colitis
Present with chronic, non-bloody, watery dhoea with no macroscopic abnormalities on scope
Commoner in women, mean age at px around 60 but 25% of cases in pts under 45
Causes frequent nocturnal dhoea and FI
Assoc with autoimmune disease eg rheumatoid, thyroid, coeliac. Can coexist with BAD in 33% of pts.
Use of NSAIDS, PPIs and SSRIs high in these patients and withdrawal can be assoc with improvement in sx
Dx in pt with c dhoea impt as specific and effective rx now available- Budesonide in controlled release preps can induce remission in both forms and also good evidence in maintaining remission in collag colitis . But up to 70% relapse and require further treatment, others remain sx free. 9-6-3.
Other drugs inc pred and immunosuppressants used in steroid refractory pts.
What kind of genetic variation makes people genetically susceptible to IBD?
SNPs (single nucleotide polymorphisms)
What percentage of someones offspring who has IBD will also develop IBD?
10%
What do genes that cause inflammatory bowel disease regulate?
Epithelial barrier
Immune response
Bacterial handling
What is the pathogenesis of IBD?
Pathogenic gut causes altered microbiota
Damaged epithelial barrier increases bacterial adhesion and translocation
Chronic inflammation occurs
What is the ratio of microbial cells in the gut lumen to eukaryotic cells in the human body?
10:1
How many different species of bacteria are present in the gut?
At least 500 different species
What is the metabolic activity of all gut bacteria equivalent to?
that of the liver
What part of the gut contains the most bacteria?
colon
What is different in the microbiota of people with IBD compared to those without?
In IBD there is a dysbosia in microbial communities
What kind of bacteria is massively more present in people with IBD than those who do not have it?
Proteobacteria
What is ulcerative colitis?
Chronic condition where the colon and rectum become inflammed
How does ulcerative colitis affect males compared to females?
Both affected the same
what is the peak incidence of UC?
Peak incidence 20 – 40 years
What are symptoms of ulcerative colitis?
Blood diarrhoea
Abdominal pain
Weight loss
Fatigue
What investigations are done for ulcerative colitis?
Bloods for markers of inflammation
Stool culture to rule out infection
Faecal calprotectin
Colonoscopy and colon mucosal biopsies
What are examples of markers of inflammation checked for in ulcerative colitis?
Normocytic anaemia
Increased CPR/platelets
Low albumin
What is considered normal faecal calprotectin?
<50ug/g of stool
What is considered elevated faecal calprotectin?
> 200ug/g of stool
What is faecal calprotectin?
Substance that is released into the intestines when inflammation is present
Where in the GI tract is inflammation due to ulcerative colitis present?
Only in the colon, starting at the rectum and working proximally
What percentage of people with ulcerative colitis require a colectomy within 10 years of diagnosis?
20-30%
What are the different levels of severity of ulcerative colities?
Mild
Moderate
Severe
Fulminant
What are characteristics of mild ulcerative colitis?
<4 stools/day sometimes with blood, normal ESR, no signs of toxicity
What are characteristics of moderate ulcerative colitis?
4-6 stools/day, occasional blood, minimal signs toxicity, CRP<30mg/L
What are characteristics of severe ulcerative colitis?
> 6 bloody stools/day and any:
temp>37.8
tachycardia>90bpm
anaemia<105g/L
ESR>30mm/h, CRP>30mg/L
What are characteristics of fulminant colitis?
10 stools/day continuous bleeding, toxicity, abdominal tenderness/distension, transfusion required, colonic dilatation on X-ray
What is proctitis?
Proctitis is inflammation of the lining of the rectum. Proctitis may be acute or chronic.
What is stool like with proctitis?
Frequency, urgency, incontinence, tenesmus
Small volume mucus and blood
Proximal faecal stasis (constipation)
What does proctitis respond to?
Responds to topical therapy
What percentage of mortality does acute severe colitis have?
2% risk of mortality, <1% specialised IBD centres
What percentage of people with acute severe colitis get an emergency colectomy at admission?
20-30% risk of emergency colectomy at admission
What do patients with acute severe colitis often look like?
These patients often look well, self caring and mobilising around ward – young with physiological reserve
What is the main differential of acute severe colitis?
10-15% present with acute severe disease – duration (>10 days), infection is main differential
What must be done within the first 24 hours of a patient being admitted with acute severe colitis?
Bloods for markers of inflammation- normocytic/microcytic anaemia
CRP/WCC/platelets
albumin
Stool culture to rule out infection
4 stool cultures for c.difficile
avoid / stop non steroidal analgesics/opiates, antidiarrhoeals, anticholinergics
IV glucocorticoids
IV hydration, correct electrolytes
LMWH
AXR
why are patients with acute severe colitis given LMWH?
3X increased risk of thromboembolism
what investigations are done for colitis
Bloods for markers of inflammation- normocytic/microcytic anaemia
CRP/WCC/platelets
albumin
Stool culture to rule out infection
Faecal Calprotectin
(0-50ug/g stool=normal, 50-200=equivocal, >200 elevated)
Colonoscopy and colon mucosal biopsies
What is Crohn’s disease?
Crohn’s disease is a lifelong condition where parts of the digestive system become inflamed.
Where can Crohn’s disease occur?
Patchy disease
mouth to anus
skip lesions
clinical features
depend on regions involved
What are clinical features of Crohn’s disease?
Diarrhoea
Abdominal pain
Weight loss
Malaise, lethargy, anorexia, N&V, low-grade fever
Malabsorption
Anaemia, vitamin deficiency
What investigations are done for Crohn’s disease?
Bloods for markers of inflammation
Stool culture to rule out infection if diarrhoea
Faecal Calprotectin (0-50ug/g stool=normal, 50-200=equivocal, >200 elevated) – may not be high if just small bowel disease
Colonoscopy with terminal ileum intubation and colon/TI mucosal biopsies
MRI small bowel study
Capsule endoscopy
Occasionally CT scan if acutely unwell and want to rule out complication eg abscess
What are differences in the histology of Crohn’s disease and ulcerative colitis?
Different histology
CD granulomas
Goblet cells depleted in UC
Crypt abscesses: UC > CD
Transmural inflammation in CD
Limited to mucosa in UC
What does PCD stand for?
perianal Crohn’s disease
What are symptoms of perianal Crohn’s disease?
Perianal pain
Pus secretion
Unable to sit down
What investigations are done for perianal Crohn’s disease?
MRI pelvis
Examination under anaesthetic (EUA)
What is the treatment for perianal Crohn’s disease?
Surgery to drain abscess and place seton stitch
Medical – antibiotics and biologic therapy (anti-TNF)
what are Extra-intestinal manifestations of IBD?
Mouth ulcers
Skin rashes/lesions
Musculoskeletal
Eyes
Primary sclerosing cholangitis
What must be considered by IBD differential diagnosis?
Other causes of chronic diarrhoea
Malabsorption eg pancreatic insufficiency, bile acid malabsorption, coeliac disease
Irritable bowel syndrome (IBS)
Overflow diarrhoea
Ileo-caecal TB
Colitis must be distinguished from
infective, amoebic and ischaemic colitis
What does chronic diarrhoea cause?
Malabsorption eg pancreatic insufficiency, bile acid malabsorption, coeliac disease
Irritable bowel syndrome (IBS)
Overflow diarrhoea
What is a possible long term complication of colitis?
Colonic carcinoma
Risk Factors
Extent
Pancolitis 26 x normal
Left colitis 8 x normal
Proctitis minimal
Duration
< 10 yrs minimal risk
20 yrs 23 x normal
30 yrs 32 x normal
How do different kinds of colitis change the risk of colonic carcinoma?
Extent
Pancolitis 26 x normal
Left colitis 8 x normal
Proctitis minimal
Duration
< 10 yrs minimal risk
20 yrs 23 x normal
30 yrs 32 x normal
What is done for IBD management?
Sub-specialty OP clinics
4/week
Proven diagnosis
Urgent IBD clinic
4 specialist IBD nurses
IBD pharmacist - Therapeutic drug monitoring
Nurse led infusion clinic
3/week
Nurse led infusion clinic
3/week
Shared care GP protocols drugs
Direct communication between GP-consultant for advice
Dedicated colonoscopy lists for surveillance with chromoendoscopy
Weekly IBD MDT –
GI consultants/trainees/IBD specialist nurses, colorectal surgeons, radiologist, dietitian, pharmacist
What kind of approach does management of IBD use?
Step up vs top down approach
What medication is given to treat Crohn’s disease by reducing inflammation?
Aminosalicylates (5-ASAs)
What are aminosalicylates?
Mesalazine
Acrylic resin
Asacol®, Ipocol®, Mesren®, Salofalk®
Ethylcellulose microgranules
Pentasa®
Pro-drugs
Balsalazide
Olzalazine
Sulfasalazine
Work by blocking prostaglandins and leukotrienes
Topical to colonic mucosa
Release mechanisms lead to colonic delivery eg pH responsive
What is the abbreviation for aminosalicylates?
(5-ASAs)
How do amionsalicylates work?
Work by blocking prostaglandins and leukotrienes
When is rectal 5-ASA given?
Induction of remission
1st line therapy
>3g orally per day
No significant improvement in remission rate
Greater and quicker clinical improvement
No increase in adverse events
Rectal 5ASA
For distal disease
Superior to rectal steroids
What do steroids induce in Crohn’s disease and ulcerative colitis?
Not effective in Crohn’s disease
Prednisolone
Optimal dose is 40mg per day
Tapering reduction over 4-8 weeks
Calcium/vit D supplementation
Budesonide
Slightly less effective than Prednisolone
Better side effect profile
How do patients ussually present with IBD and medical treatment?
flare, remission, flare
poor prognosis - more flares
what is the aim of medical treatment?
induction of remission
maintenance of remission
what are the two different approaches that may be taken for medical treatment?
step up vs top down approach
describe the stages of a step up approach
5ASA or Sulfasalazine
Prednisone/budesonide
immunomodulators
biologic agents
surgery
describe the stages of a top down approach
surgery
biologic agents
immunomodulators
prednisone/budesonide
5ASA or sulfalazine
Are aminosalicylates used in UC and chrons disease?
only UC
examples of aminosalicylates
Mesalazine
Acrylic resin
Asacol®, Ipocol®, Mesren®, Salofalk®
Ethylcellulose microgranules
Pentasa®
what are aminosalicylates first line therapy for?
induction of remission in mild/moderate UC
how are aminosalicylates taken for patients with mild/moderate UC?
> 3g orally per day
No significant improvement in remission rate
Greater and quicker clinical improvement
No increase in adverse events
when would you rectally use 5ASA
as topical therapy?
Rectal 5ASA
For distal disease
Superior to rectal steroids
what else is 5ASA first line for
Maintenance of remission
1st line therapy
Reduced number and severity of relapses
Reduced colorectal cancer risk
Lifelong therapy with >2g per day
side effects from 5ASA
nausea and diarrhoea sometimes
what is the second step up from 5ASA as medical treatment for UC and Crohns?
steroids
what are some examples of steroids used for UC and crohns disease?
Prednisolone
Optimal dose is 40mg per day
Tapering reduction over 4-8 weeks
Calcium/vit D supplementation
Budesonide
Slightly less effective than Prednisolone
Better side effect profile
what must be taken alongside prenisolone?
Calcium/vit D supplementation
what are the adverse side effects of steroids?
not for long term use/ maintence use
what treatment would you use in patients with microscopic colitis?
budesonide
what is a step up from steroids in the pyramid?
Thiopurines
what are Thiopurines primarily used for?
maintenance in UC and Crohn’s
what is an example of thiopurine
Azathioprine (6-Mercaptopurine)
what are significant side effects of thiopurine?
Leucopenia
Hepatoxicity
Pancreatitis
Possible long term lymphoma risk and non melanoma skin cancers
Up to 28% intolerant
Can check TPMT to assess suitability/aid dose target
what does a patient require while on thiopurine?
Weekly for 4 weeks and then every 8 weeks
Patients must see GP if sore throat/infection
when should a person step up from steroids to thiopurine?
patients not settling with 5ASAs
patients that have required repeated courses of steroid medication
patients that have had more than two courses of steroids in a calendar year
patients whos disease and symptoms worsen on reducing dose of steroids
those who relapse six to eight weeks after stopping steroids
is methotrexate used in both crohns disease and UC?
only crohns disease
Induction and maintenance of remission
For steroid dependant patients
10-18% intolerant
what is an issue with methotrexate particularly in young patient group?
it is teratogenic - shouldnt be used in women that arent prepared to use two forms of contraception
what do patients on methotrexate require?
specialist follow up
what is a step up from methotrexate?
biologics
what are the different groups of biologics?
Anti-TNFα antibodies
α4b7 Integrin Blockers
IL12/IL23 Blockers
what are examples of Anti-TNFα antibodies?
Infliximab (Remicade, Remsima)
8 weekly IV infusion
what are examples of α4b7 Integrin Blockers?
Vedolizumab
8 Weekly IV Infusions
what are examples of IL12/IL23 Blockers?
Ustekinumab
IV loading followed by SC 8-12 weekly
what are some newer treatments that are now available?
Tofacitinib
Small molecule
- Pan JAK inhibitor
(JAK 1 & 3)
- Oral
what is Elemental Feeding?
Exclusive elemental feeding can be as effective as steroids
More efficacious in children
Compliance difficult
in what two groups can you decide to operate?
emergency
elective
when would you operate in an emergency
acute severe colitis not responding to high dose IV steroids +/- anti-TNF biologic ‘rescue’ therapy
complications such as perforation, obstruction, abscess
when would you decide to operate in an elective procedure?
frequent relapses despite medical therapy
not able to tolerate medical therapy
steroid dependant
patient choice
what is the surgery that is down for acute severe colitis?
Subtotal colectomy
Rectal preservation
Ileostomy
remove all large bowel apart from rectal stump, patients left with stoma
following a subtotal colectomy what choices will the patient have?
“Pouch” procedure
Completion proctectomy
what is pouch surgery?
Mobilise and lengthen small bowel
use of stapler
is pouch surgery recommended in both UC and crohns disease?
no only for UC
Crohn’s can recur and cause lots of problems with pain, bleeding, fistulas, abscesses and breakdown of pouch.
what are disadvantages of pouch surgery?
patient will have to go to toilet 5 times a day, once at night
can also become inflamed, obstruction
what are surgical indications in crohns disease?
Failure of medical management
Relief of obstructive symptoms (small bowel)
Management of fistulae - e.g. bowel to bladder
Management of intra-abdominal abscess
Management of anal conditions
Failure to thrive
is surgery in crohns disease ussually curative?
Not curative – 50% need further surgery by 10 years
