Inflammatory Bowel Disease Flashcards
Which two conditions form IBD?
Crohn’s Disease
Ulcerative Colitis
What do Crohn’s and UC have in common?
Idiopathic
Chronic
Inflammatory
Where is the incidence of Crohn’s most common?
Western countries
North of Scotland
Factors Contributing to the Pathogenesis of IBD
Genetic predisposition
Mucosal immune system
Environmental triggers
Genetics in IBD
Positive family history is best established risk factor
Early onset may have stronger links
Specifically, NOD2 gene on IBD-1 of chromosome 16
Theories of IBD Pathogenesis
Pathogenic bacteria
Abnormal microbial composition
Defective host containment of commensal bacteria
Defective host immunoregulation
Environmental Factors in IBD
NSAIDs risk for IBD
Smoking =
Aggravates Crohn’s
Protective in UC
UC - Clinical Features
Peak in 20-30s
Relapsing course
Affects rectum, proximally and continuously
UC - Disease Extent
Proctitis
Left-sided colitis
Pancolitis
UC - Natural History
Variable
15% develop sever attack
of these, 30-40% will fail to respond and require surgery
UC - Symptoms
Diarrhoea + bleeding Night rising Increased bowel frequency Urgency Tenesmus Incontinence Lower ado pain (LIF) Constipation with proctitis
IBD - Important Features of History
Recent travel Antibiotics NSAIDs Family history Smoking Skin, eyes, joints
UC - Determining Severity
>6 bloody stools/24 hrs \+ 1 or more of: Fever Tachycardia Anaemia Elevated ESR/CRP
UC - Further Assessment
Albumin (inflammation detection)
Plain AXR
Endoscopy
Histology
UC - Plain AXR
Stool absent in inflamed colon
Thumb printing = mucosal oedema
Toxic megacolon = Transverse >5.5cm, caecum >9cm
UC - Endoscopy
Loss of vessel pattern Granular muscosa Contact bleeding Ulcers Poss pseudopods (mostly benign)
UC - Histology
Inflammation to mucosal layer ONLY
UC - Long Term Complication
Increased risk of colorectal cancer:
Severity
Duration
Extent
UC - Extra Intestinal Manifestations
Skin - erythema nodosum Joints - axial and peripheral pain Eyes - pain, redness Deranged LFTs Oxalate renal stones
UC - Primary Sclerosing Colangitis
Inflammatory condition affecting biliary tree
Fibrotic strictures
Histology with onion skin appearance
Mostly asymptomatic, or itch and rigors
HIGHLY increased risk of cholangiocarcinoma/colorectal cancer
Crohn’s - Onset
Earlier onset than UC
Mean age 27, but 15% before 15
Crohn’s - Distribution
Any region of GI tract
Skip lesions
Transmural inflammation
Crohn’s - Peri Anal Disease
Recurrent abscess formation Pain Can lead to fistula with persistent leakage Damaged sphincters Incontinence
Crohn’s - Natural History
25% continuous disease
50% intermittent flares
75% need surgery within 8-10 years
Crohn’s - Symptoms (Determined by Site)
Small Intestine = peri-umbilical abdo cramps, diarrhoea, weight loss
Colon = lower abdo cramps, bloody diarrhoea, weight loss
Mouth = painful ulcers, swollen lips, angular chielitis
Anus = peri anal pain, abscess
Crohn’s - Assessment
Clinical Exam = weight loss, RIF mass, peri anal signs
Bloods = CRP, albumin, platelets, B12, ferritin
Colonoscopy
Histology
Crohn’s - Histology
Cobble-staining Thickened wall Fissures Transmural Patchy GRANULOMAS
Crohn’s - Small Bowel Assessment
Barium follow through
Small bowel MRI
Technetium labelled white cell scan
Therapy - Lifestyle Advice
Stop smoking (aggravates Crohn's) Dietary factors - may influence symptoms
UC - Drug Therapy Options
5ASA (mesalazine)
Steroids
Immunosuppressants
Anti-TNF therapy
Crohn’s - Drug Therapy Options
Steroids
Immunosuppressants
Anti-TNF therapy
5ASA - Mechanism of Action
Topical effect (lessens systemic effects)
Anti-inflammatory properties
Reduces risk of colon cancer
5ASA - Side Effects
Diarrhoea
Idiosyncratic nephritis
5ASA - Routes of Administration
Oral =
Prodrugs
pH dependent release
Delayed release
Topical =
Suppositories
Enemas
5ASA - Suppositories vs Enemas
Suppositories -
Generally sufficient for proctitis
Coat lees than 20cm, but better mucosal adherence
Enemas -
Foam or liquid (patients generally prefer foam)
Less than 10% remain in rectum
Corticosteroids - Mechanism of Action
Systemic inflammatory properties
E.g. prednisolone, budesonide
Aim to reduce remission
Given as a short course with high initial dose, reducing over 6-8 weeks
Corticosteroids - Side Effects
High dependency MSK = osteoporosis, avascular necrosis GI = nausea, vomiting, bleeding Cutaneous = Acne, skin thinning Metabolic = Weight gain, diabetes, hypertension Neuropsychiatric = manic, depression, disturbed sleep pattern Cataracts Stunted growth (esp. when given to younger patients)
Immunosuppression - Use
When most potent suppression of inflammation is needed
UC = steroid sparing agents
Crohn’s = maintenance therapy
E.g. azathioprine/mercaptopurine
Immunosuppression - Mechanism of Action
Purine analogue which interferes with DNA synthesis
Can be given as a prodrug
Immunosuppression - Azathioprine
Slow onset of action (16 weeks) TPMT activity contributes to toxicity Avoid with XO inhibitors Regular blood monitoring needed Side Effects = pancreatitis, leucopaenia, hepatitis, small risk of lymphoma and skin cancer
Anti-TNFa Therapy - Mechanism of Action
TNFa = pro-inflammatory cytokine
Antibodies = infliximab, adalimumab
Promote apoptosis of activated T lymphocytes
Rapid onset of action
Anti-TNFa Therapy - Safety Issues
Infusion reactions
Infection
Cancer (lymphoma, solid tumours)
Anti-TNFa Therapy - Use
Part of long term strategy, including immune suppression, surgery, supportive therapy
Refractory/fistulising disease
Crohn’s - Surgery
Minimise amount of bowel resected
NOT CURATIVE
Repeated resection may lead to short gut syndrome and need for parenteral nutrition
UC - Surgery
CURATIVE
Permanent ileostomy or restorative proctocoloectomy and pouch
Therapy Pyramid
Smoking cessation 5ASA (UC only) Steroids if needed Immunosuppression Anti-TNFa therapy Surgery - may be best treatment in some
