Inflammatory bowel diseases including Crohns & Ulcerative colitis
|
Idiopathic chronic inflammatory disorder of the colonic mucosa, with the potential for extraintestinal inflammation.
|
The disease extends proximally from the anal verge in an uninterrupted pattern to involve all or part of the colon
|
|
UC
|
CD
|
|
|
SKIN
|
Erythema nodosum Pyoderma gangrenosum
|
Erythema nodosum Pyoderma gangrenosum
|
|
EYE
|
Iritis Episcleritis (inflammation of the episclera : white of the eye)
|
Iritis Episcleritis
|
|
KIDNEY
|
Calculi (kidney stones) Pyelonephritis (inflammation of the kidney due to bacterial infection)
|
Calculi pyelonephritis
|
|
LIVER
|
Sclerosing cholangitis (inflammation of bile ducts: impeding bile flow)
|
Systemic amyloidosis (deposition of amyloid proteins)
|
|
JOINTS
|
Seronegative polyarthritis (blood test –ve for rheumatoid factor protein and cyclic-citrulinated peptide)
|
Seronegative polyarthritis
|
|
Endoscopy and biopsy
|
Flexible sigmoidoscopy or Colonoscopy
|
|
Radiology
|
Contrast enhanced ultrasound, Barium studies, CT, MRI, Capsule endoscopy
|
|
Mild-Moderate disease
|
5-Aminosalicylates (suppository or enema possibly combined with oral aminosalicylates) If unable to tolerate aminosalicylates: Steroids (topical corticosteroid or oral prednisolone)
|
|
Resistant Disease
|
Immunosuppressants (eg Azathioprine, Mercaptopurine) Anti-TNF monoclonal Ab (Infliximab, Adalimumab)
|
|
Severe colitis
|
Intravenous corticosteroids Ciclosporin Infliximab (5 mg/kg infused over 2 hours at 2 and 6 week intervals) (Assuming 3 doses, average cost per patient = £5,035) Surgery
|
|
Indicated for severe or refractory IBD
|
Thiopurines. Methotrexate. Ciclosporin.
|
|
BSG guidelines advise use in following situations
|
Severe relapse or frequently relapsing disease. 2 or more steroid course required within 12 months. Relapse below 15mg prednisolone. Relapse within 6 weeks of stopping steroids.
|
|
Mild:
|
Topical Steroids: Aminosalicylates
|
|
Moderate:
|
Infliximab, Systemic Corticosteroids, Oral steroids
|
|
Severe:
|
Surgery, Cyclosporine, Infliximab
|
|
Superficial diffuse inflammation in the lamina propria affecting the colon only
|
|
|
Characteristics
|
Continuous from the rectum up to the caecum
|
|
Crypt abscesses, goblet cell depletion and crypt distortion
|
|
|
Can affect the distal few cm of small bowel – ‘backwash ileitis’
|
|
|
Non-smokers
|
|
|
The most intense inflammation begins :
|
the lower right in the sigmoid colon and extends upward and around to the ascending colon. At the lower left is the ileocecal valve with a portion of terminal ileum that is not involved.
|
|
Repeated ulceration and healing cycles result in:
|
Granulation tissue resembling polyps
|
|
Small Bowel
|
80% of cases small bowel involved. Majority distal ileum. 1/3 exclusively ileitis.
|
|
Ileo-colonic
|
50% have ileocolitis
|
|
Colonic
|
20% colonic disease only
|
|
Anus
|
33% have anal disease. Other (gastroduodenal, oesophageal, oral). Rare.
|
|
Inappropriate immune response
|
Increased pro-inflammatory cytokines eg TNF-α, IL-1β, IL-6
|
|
Breakdown in tolerance to gut microbial load
|
Altered gut flora. Defects in mucosal immunity.
|
|
Combination of factors
|
Enviromental factors. Triggered by particular bacterial pathogen.
|
|
Genetic – increased risk in twins/other relative
|
|
|
Diet
|
|
|
Smoking
|
|
|
Genetics
|
47 loci associated with UC (and counting)
|
|
Initial diagnosis if mild to moderate:
|
5-ASA’s less effective but may have a chemoprotective effect against cancer risk. Glucocorticosteroids
|
|
Severe active Crohn’s (including fistulising Crohn’s)
|
Immunosuppressants Azathioprine, Mercaptopurine, Methotrexate Anti-TNF therapy (Infliximab) (sever active Crohn’s)
|
|
For perianal Crohn’s:
|
Antibiotics (Metronidazole, Ciprofloxacin) –
|
|
Side effects
|
Nausea
|
Advise patients to take it at night
|
|
Allergic reaction
|
Fever/Rash/Arthralgia
|
|
|
Myelosuppression
|
||
|
Hepatotoxicity
|
||
|
Pancreatitis
|
||
|
Monitoring
|
FBC/LFT every 2 weeks for first 2 months, Then every 4-8 weeks up to ~6/12, Then every 3/12
|
|
|
Tremor
|
|
Paraesthesia
|
|
Malaise
|
|
Headache
|
|
Abnormal liver function tests
|
|
Hirsutism
|
|
Gingival hyperplasia
|
|
Idiopathic chronic inflammatory disorder of the full thickness of the intestine
|
Most commonly the ileum and the colon, with the potential to involve the gastrointestinal tract at any level from the mouth to the anus and perianal region.
|
|
Typically there is patchy disease in the gastrointestinal tract
|
with intervening areas of normal mucosa “Skip lesions”
|
|
Transmural inflammation with lymphoid aggregates
|
(clusters of lymphoid cells- include T-cells, B-cells and NK cells.)
|
|
Non caseating granulomas (60% cases)
|
Caseating “turning to cheese”
|
|
Skip Leisons
|
|
|
*Strictures and fistula formation
|
In Crohn’s, strictures make the bowel too tight, and fistulas create unnatural pathways—both are serious complications.
|
|
Perianal disease
|
|
|
Can affect any part of the GI tract
|
|
|
Smokers
|
|
|
Crohn's disease
|
Ulcerative Colitis
|
|
Incidence 8-10/100,000 in UK Prevalence ~150 per 100,000 (1 in 660 people)
|
Incidence 15/100,000 in UK Prevalence 200 per 100,000 (1 in 500 people)
|
|
Crohn's Colitis
|
|
|
Infective colitis:
|
E.coli
|
|
Campylobacter
|
|
|
Salmonella
|
|
|
Yersinia
|
|
|
Amoebic Dysentery
|
|
|
Ischaemic Colitis
|
|
|
*Pseudomembranous Colitis
|
Clostridium difficile infection
|
|
Oral
|
Prednisolone (eg 40mg od, 8 week reducing course). Budesonide (lower systemic effects). Beclomethasone (Clipper). Used for moderate flares of UC/Crohn’s.
|
|
Intravenous:
|
For severe UC or Crohn’s Hydrocortisone (eg 100mg qds)
|
|
Topical
|
Steroid Suppositories/Enemas (eg Predsol supps, Predfoam enemas). Less effective than topical 5-ASA but can be used in combination.
|
|
Side effects:
|
Skin thinning. Osteoporosis. Osteonecrosis Easy bruising. Cushing’s syndrome (moon face, acne, hirsutism, striae). Cataracts. Diabetes. Hypertension. Psychosis.
|
|
Ciclosporin
|
Inhibits dephosphorylation of nuclear factor of activated T cells (NFATc)
|
|
|
Tacrolimus (FK506)
|
Binds to FK-506 binding protein (FKBP). Calcineurin inhibitor.
|
|
|
Both prevent
|
interleukin 2 release and clonal expansion of T cell subsets
|
|
|
Crohn’s & Ulcerative Colitis
|
|
|
Salicylates
|
|
|
5-Amino salicylic acid (5-ASA); mesalamine (Asacol)
|
|
|
Steroids (glucocorticoids): Methylprednisolone (Medrol)
|
|
|
Immunosuppressants: Azathioprine & mercaptopurine
|
|
|
Ciclosporin A (Sandimmun or Neoral) Tacrolimus (FK-506, Fujimycin) (Prograf, Advagraf, Protopic)
|
|
Inflammatory cells (the bluish infiltrates) extend from mucosa through submucosa and muscularis.
|
|
|
On the serosal surface inflammatory cells appear as nodular infiltrates with pale granulomatous centres.
|
|
Ulcerative colitis
|
Crohn's disease
|
|
Affects the colon only
|
Affects any part of the GI tract
|
|
Male:Female 1:1
|
Male: Female 1:2
|
|
Bloody diarrhoea Abdominal pain
|
Abdominal pain Weight loss Perianal disease Bloody diarrhoea
|
|
Continuous, always begins in rectum
|
Skip lesions
|
|
No strictures
|
Stricture and fistula formation with perianal disease
|
|
Mucosal inflammation Diffuse inflammation in the lamina propria Patchy ulceration with crypt abscesses, goblet cell depletion and crypt distortion
|
Transmural inflammation throughout bowel wall, lymphoid aggregates and non-necrotising granulomas. Can develop fissuring ulcers, crypt abscesses, goblet cell depletion and crypt distortion
|
|
Terminal ileum in 10% cases
|
Often affects the terminal ileum (80%) Any part of alimentary tract can be affected
|
|
No fistulas
|
Fistulas
|
|
‘Bloody diarrhoea’ and passage of mucus
|
|
|
Urgency
|
|
|
Abdominal Discomfort (pain unusual)
|
|
|
Usually insidious onset
|
|
Typical Features:
|
Abdominal Pain. Diarrhoea. Weight loss. Anorexia.
|
|
5 Aminosalicylic acid (Mesalazine)
|
Moderate inflammatory cells and cytokine release from epithelial cells. Mechanism not fully understood but involves inhibition of cyclooxygenase and prostanoid formation and N-acetyl-5-ASA through PPAR gamma (Peroxisome Proliferator Alpha Receptor gamma)
|
|
Uses - UC
|
Maintainence of remission – mainstay of long-term treatment for UC. Treatment of mild-moderate flares. Chemoprotective effect against colorectal cancer.
|
|
Uses – Crohn’s
|
Limited effectiveness compared to UC. Limited effectiveness in active Crohn’s or maintaining remisson. May reduce risk of relapse after surgery.
|
|
Side Effects:
|
Diarrhoea! Nausea. Headache Rash (rarely Stevens-Johnson syndrome). Nephrotoxicity (Interstitial nephritis & Nephrotic syndrome). Agranulocytosis (low white blood cell count). Pancreatitis.
|
|
Ulcerative Colitis
|
Crohn's Disease
|
|
Only affects colon
|
Affects mouth to anus
|
|
No fissures, horizontal ulcers
|
Deep ulcers & fissures
|
|
Malignant change common
|
Malignant change rare
|
|
Fistulae less common
|
10% have fistulae
|
|
25% have anal involvement
|
60% have anal involvement
|
|
Muscular shortening of the colon
|
Fibrous shortening
|
|
No skip lessons
|
Skip lesions
|
|
No fat or vitamin malabsorption
|
Fat & vitamin malabsorption
|
|
No granulomas (collection of macrophages)
|
Granulomas in 50%
|
|
Mild lymphoid reaction
|
Marked lymphoid reaction (increased WBC)
|
|
Mild fibrosis
|
Fibrosis
|
|
Mild Serositis
|
Serositis (inflammation, serous membranes)
|
|
Raised ANCA (antineutrophil cytoplasmic antibodies. Autoantibodies directed against own neutrophils.)
|
ANCA normal
|
|
More common in non-smokers or ex smokers
|
Increased incidence in smokers
|
No comments yet.
Cheatography n. The art of mapping complex subjects into clear, instantly navigable reference guides.
