What is ulcerative colitis?
Diffuse mucosal inflammation limited to the colon
What is ulcerative colitis defined by?
Distal colitis limited to rectum (proctitis) or rectum and sigmoid (proctosigmoiditis)
Left sided colitis to splenic flexure
Extensive colitis to hepatic flexure
What is Crohn’s disease?
Patchy, transmural inflammation affecting any part of the GI tract
What is Crohn’s disease defined by?
Location - colonic, terminal ileum, perianal
Pattern of disease - inflammation, stricturing and fistulating
Which gender is more likely to get which disease?
Slight female predominance - Crohn’s
Slight male predominance - ulcerative colitis
Briefly describe the epidemiology of both diseases.
Diseases of young people
- 10-40 years, peak incidence
- 15% present over the age of 60
What is the pathogenesis of both diseases?
Unknown Host response to environmental triggers in genetically susceptible individuals Genetic factors implicated Smoking - increases risk of Crohn's - reduces risk of ulcerative colitis
What would you ask for in the history when you suspect an IBD?
Stool frequency, consistency, urgency, blood
Abdominal pain, malaise, fever
Extraintestinal symptoms (joint, eyes and skin)
What skin conditions can be associated with IBD?
Erythema nodosum (shins commonly)
- mostly UC
What eye conditions can someone with IBD get?
What mouth problems can someone with IBD get?
- particularly Crohn’s
What do you expect to see on perineal examination in someone with Crohn’s disease?
If you suspect someone has IBD, what initial investigations should you do?
FBC, ESR U&Es, LFTs CRPs Stool cultures for C.Diff toxin Faecal calprotectin - non-specific, but if low, it exclude inflammation Abdominal X-Ray
If you suspect someone has IBD, what in depth investigations should you do?
Rigid sigmoidoscopy Colonoscopy - used most Avoid endoscopic examination in severe disease (bad symptoms) Small bowel radiology/MRI Labelled WCC scanning
Describe the colon appearance in ulcerative colitis.
Granular mucosa Not much ulceration Lack of definition of the blood vessels Contact bleeding Luminal pus
Describe the appearance of the intestines in Crohn’s disease.
Ulceration - fissuring ulceration Patchy involvement of the colon or ileum - not the rectum Cobblestone appearance - areas of ulceration separated by narrow areas of healthy tissue
What are the treatments for ulcerative colitis?
5ASAs if needed
What are the treatments for Crohn’s disease?
Corticosteriods Thiopurines Biologics Methotexate Immune modulating diet
What corticosteriods are used for IBD treatment?
- IV hydrocortisone
- IV methyloprednisolone
- oral prednisolone
How are steriods given and why in IBD?
They are given high dose at first to rapidly induce remission, then they are put on a slowly reducing course, to allow mucosal healing
- because steroids can’t maintain remission
- prednisolone 40mg/day for 1 week
- reduce by 5mg/week
What are the possible side effects of steroid use?
Immunosuppression Impaired glucose tolerance Osteoporosis Weight gain Cushingoid appearance
What is 5ASAs?
Mesalazine - 5-aminosalicylate (5ASA) Different methods of release - pH dependent release/renin coated - time controlled release - delivery by carrier molecules Can be effective as a topical therapy for distal disease - suppositories and enemas - good for symptomatic proctitis
What are aminosalicylates?
Anti-inflammatory product used to treat ulcerative colitis
What is the function of aminosalicylates?
Induction of remission in mild/moderate ulcerative colitis
Maintenance of remission
Efficacy relies on compliance
Maintenance therapy reduces cancer risk
What are the benefits of high doses of aminosalicylates?
Higher remission rates
Better mucosal healing
What are the side effects of
Renal impairment (interstitial nephritis, nephrotic syndrome) - rare and idiosynchratic Sulphasalazine (related to mesalazine) - commonly badly tolerated Intolerance
What are thiopurines and when are they used?
Steroid sparing agent
- used when patients require 2 or more steroid course a year
- have experienced relapse on less than 15mg prednisolone
What are thiopurines used for?
Maintenance therapy for ulcerative colitis and Crohn’s disease
Post-op prophylaxis in complicated Crohn’s
Describe the pathophysiology of thiopurines.
Immune modulting drugs
Prevent T-cell clonal expansion in response to an antigenic stimuli and allows T-cell apoptosis
Name some thiopruines.
What is TMPT?
It’s an enzyme that metabolises mercaptopurine to one of it’s metabolities
- reduced levels, reduces effect of immunosuppession
What are the metabolites of mercaptopurine measured in therapeutic drug monitoring?
MeMP - methylmercaptopurine
- levels predict risk of a drug induced hepatitis
6TS - thioguanine nucleotide
- active metabolite, used for adjusting levels and checking compliance
What are the common side effects of Thiopurines?
Leucopenia Nausea, vomiting (1 in 5) Arthralgia Pancreatitis Hepatitis (reversible) Squamous skin cancers - be careful in the sun, use sun cream Haematological malignancy (slight)
What is methotrexate?
Folate scavenger - need folate supplements
Used in Crohn’s when they can’t tolerate Thiopurines
What are the side effects of methorextare?
GI upset Hepatotoxicity Immunosuppression Sepsis Pulmonary fibrosis Teratogenic
When would Infliximab be used?
Severe or fistulating Crohn’s disease
Rescue acute severe ulcerative colitis
Moderate severe ulcerative colitis that doesn’t respond to other treatment
What is Infliximab?
A mouse anti-TNF monoclonal antiboidy
- prevents macrophage activation
- switches off inflammatory process in the mucosa
How is Infliximab administered?
Loading regime at 0/2/6 weeks
2 month IV infusions thereafter
- maintenance therapy
What are the complications associated with Infliximab?
The body may recognise it as foreign (mouse Ab) and produce antibodies
- loss of efficacy
- allergic reactions
What is Adalumimab?
Humanised anti-TNF alpha monoclonal antibody
What is the benefit of Adalumimab?
People are less likely to have a reaction compared to Infliximab
What is Golimumab?
Humanised anti-TNF alpha
What is Golimumab used for?
Moderate to severe ulcerative colitis
- less so for Crohn’s
With all anti-TNF drugs, what are the complications?
Infection risk - reactivation of TB - reactivation of Hep B Neurological - incidence of MS - progressive multifocal leucoencephalopathy Malignancy - possible increased lymphoma risk
What is Vedoluzimab?
A new biologic
- binds integrin (a lymphocyte adhesion molecule)
What is acute severe colitis?
Patients who fail to respond to optimal treatment with 5ASA/prednisolone or with severe disease warrant hospital admission
How is acute severe colitis?
IV steroid therapy
Liaison with colorectal surgeon
- stool frequency >8 day
- or CRP >45 on day 3 predicts colectomy in 85%
What obs/blood results suggest acute severe colitis?
>6 bowel movements per day Frequent PR blood Raised temperature pulse >90 < 10 Hb - anaemia ESR >30
What investigations should you do if someone has suspected acute severe colitis?
Daily FBCs, ESR, U&Es and CRP Stool cultures - C.Diff - high incidence of infection Daily abdominal X-Ray Sigmoidoscopy - if it is a new presentation
How is acute severe colitis treated?
Prophylactic LMWH heparin
- high risk of DVTs
IV hydrocortisone 100mg or methylprednisolone 30mg
Treat for 72 hours and if they improve, they can be given oral steroids
- if they don’t they need rescue therapy
What is rescue therapy in acute severe colitis?
Infliximab single dose
- if medical therapy doesn’t work
What is the surgery done in ulcerative colitis?
Ileo-anal pouch (don’t need a stoma) or ileostomy
When is surgery done in Crohn’s disease?
Indicated for stricturing, perforation, fistulising disease