IBD Flashcards
What is IBD/
umbrella term for two main diseases causing inflammation of the GI tract: Ulcerative Colitis and Crohn’s disease. They both involve inflammation of the walls of the GI tract and are associated with periods of remission and exacerbation.
Whats the prevalence of Crohn’s disease?
25-100/100,000
Whats the prevalence of ulcerative colitis?
80-150/100,000
Where are the highest incidence rates of IBD?
Northern Europe, UK, North America
How does race and ethnic group impact the incidence and prevalence of IBD?
Rates are lower in Hispanic and Asian people compared with White individuals
Jewish people are more prone to IBD than any other ethnic group
What age is IBD usually diagnosed?
Crohns - 15-35
UC - 15-35 and 60-80
Whats the aetiology of IBD/
Unknown but known interaction between genetic susceptibility, environment, intestinal microbiota and host immune response
What are the genetic factors of IBD?
Up to 1/5 pt with CD and 1/6 pt with UC will have a 1st degree relative with the disease
NOD2 gene
T cell autoimmune
What are the environmental aetiological factors of IBD?
Smoking - smoking can exacerbate CD and increase risk of disease recurrence after surgery. Nicotine has been shown to be an effective treatment in those with UC
NSAIDs- associated with onset and flare ups of IBD
Poor hygiene - lower risk of developing CD (i.e. decreased microbial exposure as a child increase risk)
Nutritional factors - studies are equivocal but high sugar/fat and low fibre intake may play a role. Breast-feeding can provide protection against development of IBD
Psychological - chronic stress and depression
Appendicectomy - protective against development of UC but increases risk of CD
Antibiotic use may increase risk
How may intestinal microbiota relate to aetiology of IBD?
Those with IBD have a reduced diversity of microbial species
Increased E.coli adherence to ileal epithelial cells in CD
Bacterial antigens
Defective chemical barriers or intestinal defensin
Impaired mucosal barrier function
Where in the bowel does Crohn’s disease affect?
Any part of GI tract from mouth to anus but has a particular tendency to affect the terminal ileum and ascending colon
It can involve one small area of the gut, such as the terminal ileum, or multiple areas with skip lesions. It may also involve the whole of the colon
What is total colitis?
When UC affects the whole of the colon also known as pancolitis
What is proctitis?
When UC affects the rectum alone
What is left-sided colitis?
When UC affects the sigmoid and descending colon
What is extensive colitis?
When UC affects the whole colon
What is backwash ileitis?
Up to 35% of patients with UC develop inflammation in the terminal ileum, which historically, has been attributed to backwash of colonic contents into the terminal ileum
It’s a result of an incompetent ileoceacal valve
What is proctosigmoiditis?
UC affecting rectum and sigmoid colon
What macroscopic changes can be seen with Crohn’s disease?
Bowel appears bright red and swollen
Later small, discrete aphthoid ulcers with a haemorrhagic rim form
Later deeper longitudinal ulcers form which may develop into deep fissures involving the full thickness wall of the GIT
Fibrosis may follow with stricture formation
Mucous membrane appears cobble-stoned
Aggregations of inflammatory cells and lymphocytes infiltrate the bowel wall
Mesenteric lymph nodes may be enlarged (reactive hyperplasia)
Granulomas may be present in lymph nodes
What macroscopic changes can be seen in ulcerative colitis?
Mucosa looks reddened and inflamed
Mucosa is very friable
Shallow ulceration and marked pseudo-polyps
What microscopic changes are seen in Crohn’s disease?
Inflammation is transmural of the bowel
There is an increase in chronic inflammatory cells and lymphoid hyperplasia
In 50-60% of pt, granulomas are present (non caseating epitheliod cell aggregates with Langerhans giant cells)
Increased goblet cells
What microscopic changes are seen in ulcerative colitis?
Inflammation is superficial and limited to the mucosa (unless fulminant)
Chronic inflammatory cell infiltrate in the lamina propria
neutrophils migrate through the walls of glands to form crypt abscesses
depletion of goblet cells and mucin from gland epithelium
granulomas are infrequent
What serological testing can be done to distinguish between ulcerative colitis and Crohn’s disease?
Anti-saccharomyces cerevisiae antibody (ASCA) in crohns patients
Perinuclear anti-neutrophil antibodies (pANCA) in ulcerative colitis
What are extraintestinal manifestations of IBD/
Joint complications are most common - arthropathyes, arthralgia, ankylosis spondylitis, inflammatory back pain
Eyes - uveitis, epicleritis, conjunctivitis
Skin - erythema nodosum, pyoderma gangrenous
Liver and biliary tree - primary sclerosing cholangitis (UC), fatty liver, chronic hepatitis, cirrhoses
gallstones (crohns)
Anaemia + vit B12 deficiency
Nephrolithiasis (crohns)
Venous thrombosis
What are the clinical features of Crohn’s disease?
diarrhoea (can be bloody), abdominal pain (more predominant) and weight loss
Constitutional symptoms - malaise, lethargy, anorexia, nausea, vomiting, low-grade fever, peri anal disease, angular stomatitis, aphthous ulcers
Note that in 15% of pt there are no GI symptoms
What may be the predominant clinical features of Crohn’s disease in children?
Reduced growth velocity delayed puberty
What proportion of pt will require an intestinal resection within 5 years of diagnosis?
50%
What are the characteristics of the abdominal pain in crohns?
May be colicky
Usually has no special characteristics
May be only mild discomfort
Usually right lower quadrant
What portoprion of those with crohns are affected by diarrhoea and what are the characteristics of it?
80%
In colonic disease it usually contains blood - this makes it difficult to differentiate from UC
May be steatohepatitis in small bowel disease
How does Crohn’s disease first present?
Very variable
It can present insidiously or as an emergency - sometimes it present with acute right iliac fossa pain which mimics appendicitis
What physical signs of crohns may be seen on examination?
Weight loss
Signs of malnutrition
Aphthous ulceration of mouth
Angular stomatitis
Pyrexia
Dehydration
Pallor
Tachycardia
Hypotension
Tenderness or mass in abdomen (inflamed loop of bowel or abscess)
Anus may have oedematous anal tags, fissures or peri anal abscesses
Examine for extraintestinal features too e.g. joints, skin, eyes etc
What are significant blood tests for crohns?
Anaemia
Raised ESR and CRP
Raised white cell and platelet counts
Hypoalbuminaemia
Liver biochemistry may be abnormal
Blood cultures if septicaemia suspected
Serological tests - negative perinuclear ANCA and positive ASCA
What anaemia may be present in crohns?
Normocytic, normochromic anaemia of chronic disease
Deficiencies of iron and or folate can also occur
(Anaemia due to B12 deficiency is unusual although serum B12 can be below normal range)
Why may hypoalbuminaemia be present in crohns?
It’s part of an acute phase response to inflammation associated with a raised CRP
What stool tests should be done for suspected Crohn’s ?
C.diff toxin assay whenever diarrhoea is present
Microscopy for parasites if relevant travel history
Fecal calprotectin and lactoferrin raised in active intestinal disease
What stool test is useful for disease monitoring in IBD?
Faecal calprotectin
What imaging should be done for suspected crohns?
Colonoscopy if colonic involvement is suspected except in severe disease
Upper GI endoscopy to exclude oesophageal and gastroduodenal disease
Small bowel imaging e.g. barium follow-through, CT with oral contrast, small bowel ultrasound or MRI enteroclysis
Maybe ultrasound scanning to reduce radiation exposure
Perianal MRI or endoanal ultrasound to evaluate perianal diseae
Capsule endoscopy when radiological examination is normal
What are the general considerations for managing Crohn’s?
To induce and maintain clinical remission
To achieve mucosal healing in order to prevent disease progression and complications
Pt with mild symptoms and no evidence of extensive disease may require symptomatic treatment only
Smoking should be stopped
Anaemia should be treated
Treat any deficiency from malabsorption with vits and minerals
Most are treated as outpatients although severe attacks may require admission and prophylaxis for thromboembolism should be given to all inpatients.
How big is the risk of thromboembolism in IBD?
3-4 times higher risk of developing a blood clot than those without IBD
What drugs are used to induce remission in crohns?
Monotherapy with conventional glucocorticosteroid - prednisolone
Consider enteral nutrition as an alternative for children who have concerns about SE e.g. growth
Consider budesonide for mild-moderate ileocaecal CD
Consider aminosalicylate treatment if glucocorticosteroids cannot be used e,g, mesalazine of sulfasalazine
Moderate-severe CD - may consider early introduction of immunosuppressive therapy e.g. azathioprine (wont help in inducing remission though)
What add-on treatment can be used for inducing remission in crohns?
Azathioprine or mercaptopurine - add onto steroids or budesonide (if 2 or more inflammatory exacerbations in 12 months or steroid dose can’t be tapered)
Methotrexate - add onto steroids or budesonide if can’t tolerate above
What can be given to induce remission in Crohn’s disease in those with severe active disease which hasn’t responded to conventional therapy?
Infliximab and adalimumab
What type of drug is budesonide?
A controlled-release corticosteroid
What is exclusive enteral nutrition?
replacing all food and drinks with specialised liquid nutrition formula and water.
If administered as the sole source of nutrition for 28days, rates of induction of remission are similar to those obtained with steroids.
Not often used in adults due to issues with compliance to diet
What type of drug is azathioprine?
An immunosuppressant
What type of drug is infliximab and adalimumab?
Anti-TNF agents
What factors suggest a good prognosis of Crohn’s?
Older age at diagnosis
No perianal disease
Not needing steroids at first presentation
Not isolated terminal ileitis
Limited ulceration at index investigations
Non-smoker
Whats the goal of maintenance therapy in crohns?
Prevent disease progression
Reduce the need for corticosteroids as they have a high burden of SE
What drugs are used for mainatence of remission of crohns?
Long term treatment with azathioprine or mercaptopurine
Methotrexate 2nd line
Anti-TNF antibodies e.g. infliximab or adalimumab
What should be checked before starting treatment of azathioprine or mercaptopurine? Why?
Levels of this purine methyltransferase (TPMT)
This is the key enzyme involved in their metabolism and this enzyme has significant genetic variation and deficiencies can result in high circulating levels of thioguanine nucleotides which increase risk of bone marrow depression
(3 monthly blood counts should be checked throughout treatment)
What proportion of Crohn’s pt will require an operation at some time during the course of their disease?
80%
What are the indications for surgery for crohns?
Failure of medical therapy, with acute or chronic symptoms producing ill-health
Complications e.g. perf, abscess, toxic dilation
Failure to grow in children despite medical treatment
Presence of perianal sepsis
What surgery is done for pt with small bowel disease in Crohn’s?
Stricturoplasty
Resection and anastomosis
What surgery is done when colonic Crohn’s disease involves the entire colon and the rectum is spared/minimally involved?
a subtotal colectomy and ileorectal anastomosis may be performed.
What surgery is done for Crohn’s disease if the whole colon and rectum are involved?
A panproctocolectomt with an end ileostomy
Whats the recurrence rate for Crohn’s disease after surgery?
Up to 80%
How is remission maintained in Crohn’s disease after surgery?
Azathioprine or metronidazole as mono therapy to maintain remission when previously used with a conventional glucocorticosteroid to induce remission and in those who have not
Consider methotrexate to maintain remission only if they needed methotrexate to induce remission or have tried but didn’t tolerate aza or mercaptopurine or there are contraindications e.g,. Deficient TPMT activity or previous episode of pancreatitis
Consider infliximab or adalimumab
How are strictures managed in Crohn’s disease?
Balloon dilation
How should pt with Crohn’s disease be followed up after surgery?
They should undergo an ileocolonoscopy to assess the anastomosis for disease recurrence 6 months after surgery
What proportion of those with crohns have evidence of small bowel disease?
80%
When a pt with crohns has evidence of s,all bowel disease, where does it most commonly occur?
Terminal ileum
What proportion of those with Crohn’s disease have perianal Crohn’s disease? What is this?
33%
This includes a variety of conditions that affect the perianal area (e.g. skin tags, fissures, fistulae, abscesses, or anal canal stenosis).
Whats the mneumonic for microscopic and macroscopic changes seen in Crohn’s disease?
Cobblestone appearance
Rose thorn ulcers
Obstruction
Hyperplasia (lymph nodes)
Narrowing lumen
Skip lesion
What are the complications of Crohn’s disease?
Psychosocial
Intestinal - structures, stenosis, abscess formation, fistulas, perianal disease (e.g. skin tags, fissures), perforation
Anaemia
Lymphadenopathy
Malnutrition/malabsorption where large areas of small intestine are affected
faltering growth and delayed pubertal development
Colorectal cancer
How can IBD affect fertility?
If you have active IBD, especially Crohn’s, you may have a slightly lower chance of conceiving. Severe inflammation in the small intestine can affect the fallopian tubes and make it more difficult to get pregnant.
What is a strictureplasty?
A way to treat strictures and blockages in the small intestine without removing any gut
The surgeon opens up the narrowed section of the intestine with a lengthwise cut, and then reshapes it by closing it up the opposite way. Food can then pass freely through the reshaped section of the intestine.
What is an endoscopic balloon dilation?
For very short strictures that are accessible by colonoscopy, it may be possible to have an endoscopic balloon dilation. In this procedure, an endoscope with a balloon attached is used to widen the narrowed part of the intestine
What is a resection and when will it be used?
If the stricture is long, or there are several strictures close together, a resection may be preferable to a strictureplasty. In a resection the surgeon removes the damaged part of the gut, and then anastamoses together the ends of the remaining healthy sections
What is a hemicolectomy?
A partial Colectomy - half the colon
Used if only half the colon is affected
What is a colectomy with ileostomy and when is it used?
For those with severe Crohn’s Disease in the large intestine or colon, it may sometimes be necessary to remove most or all of the colon (a colectomy).
The surgeon then brings the end of the small intestine out through an opening in the wall of the abdomen. This is an ileostomy or stoma. A bag is fitted onto the opening to collect waste.
What is a Colectomy with ileo-rectal anastamosis and when is it used?
Sometimes when the rectum has remained healthy it may be possible to have a colectomy with ileo-rectal anastomosis. In this operation the colon is removed, but instead of creating an ileostomy, the surgeon joins the end of the ileum (small intestine) to the rectum. This operation is not advisable if the rectum
is severely inflamed or scarred, or if the anal muscles have been damaged. Without a colon the faeces tend to be very liquid, and people with this type of anastomosis may need to empty their bowels more frequently.
What is a proctocolectomy and ileostomy?
If the rectum is also affected by inflammation it may have to be removed along with the colon and the anal canal, in an operation known as a proctocolectomy.
The surgeon will then create an ileostomy in the same way as for a colectomy. This form of surgery is irreversible, but means that you no longer have a colon to become inflamed or develop bowel cancer
What is a laparoscopy?
Making 4-5 small incisions about 1cm each long
Smal tubes are passed thigh and a gas is used to inflate the abdomen slightly and give the surgeon more space
A laparoscope (thin tube with light and camera) is used to relay images of the inside of the abdomen to a video screen and small surgical instruments are guided to the right place using this view
What are the advantages of laparoscopic operations?
Less pain after op
Smaller scars
Faster recovery
Reduced risk of a wound infection. Or hernia
Shorter stay in hospital
What is a stoma?
the intestine is brought to the surface of the abdomen, and an opening is made so that digestive waste (liquid or faeces) drain into a bag rather than through the anus. If the part of the intestine brought to the surface is the ileum, this is known as an ileostomy. If the large intestine or colon is brought to the surface and connected in a similar way, it is a colostomy. Both types of opening are also called stomas.
Most stomas are about the size of a 50p piece, and pinkish red in colour. Because the contents of the small bowel are liquid, and might irritate the skin, an ileostomy usually has a short spout of tissue, about 2-3cm in length. Depending on the type of stoma bag used, ileostomy bags usually have to be emptied 4-6 times a day, and changed 2-5 times a week. Colostomies pass firmer stool, so colostomy bags are usually emptied slightly less frequently (1-3 times a day), and may need to be changed each time.
What are the advantages of surgery for IBD?
• relief from pain
• lessening of symptoms such as diarrhoea, vomiting and fatigue
• being able to reduce or even stop taking drugs which may be causing side
effects
• the ability to eat a more varied diet and to gain weight more easily
What immunosuppressants are used for IBD?
Thiopurines - azathiopurine pr 6-mercaptopurine
Methotrexate
Cyclosporine and tacrolimus
Ozanimod
Whats the moa of thiopurines?
These kill T cells by blocking the TCR pathway responsible for cell survival
They also block the ability of inflammatory cells to build DNA by inhibiting production of purines = prevents production of inflammatory cells
Whats the moa of methotrexate?
It inhibits dihydrofolate reductase = reduces production of DNA, RNA, thymidylates and proteins = lower levels of inflammation
Whats the moa of cyclosporine and tacrolimus?
They block calcineurin - protein responsible for T cell = fewer active T cells = less inflammation
When is cyclosporine used for IBD?
only rarely for people with severe colitis who are hospitalized.
What are adverse effects of azathioprine and 6-mercaptopurine?
nausea
allergic reactions
acute pancreatitis
hepatitis
increased risk of infection,
small but increased long-term risk of developing lymphoma and non-melanoma skin cancer
myelosuppression
What are adverse effects of methotrexate?
Hepatotoxicity
Pneumonitis
Increased risk of infection
Malignant
Alopecia
Stomatitis
Myelosuppresson
Allergic reaction
Teratogenic
(Note should be taken with folic acid!)
What is indeterminate colitis?
The name indeterminate colitis is given when it’s unclear if a person has Crohn’s disease or ulcerative colitis (UC). It is thought that around 15% of people with inflammatory bowel disease (IBD) are initially given this diagnosis.
What proportion of patients with crohns will require a surgical resection within the first 5 years of disease?
Up to 50%
Up to 50%
What are the clinical features of ulcerative colitis?
Diarrhoea with blood and mucus
Lower abdominal discomfort (less predominant)
Tenesmus and urgency
Malaise, lethargy, anorexia with weight loss (these symptoms tend to be less severe than with crohns)
Aphthous ulcers in the mouth may be seen
Whats the course of ulcerative colitis?
Relapsing and remitting
Whats the most common form of IBD?
Ulcerative colitis
Whats the epidemiology of ulcerative colitis?
240 per 100,000
More commo in females
Bimodal peak in incidence between 15-25 and 55-65
What proportion of those with ulcerative colitis will have proctitis only?
50%
What proportion of those with ulcerative colitis will require surgery?
25%
What are the aetiological factors for ulcerative colitis?
The current theory is of an abnormal immunological response and/or increased reaction to commensal bacteria within a genetically susceptible individual.
This theory is based around three core aetiological factors: immunity, genetics and the environment.
Immunity - disrupted micro flora immune response.
Genetics - susceptible loci, positive FHx, HLA gene associations
Environment - smoking is protective, milk consumption and certain meds e.g. NSAIDS has been linked
What is pancolitis? If you have it what are you at risk of?
Inflammation of the entire colon
Risk of developing backwash ileitis
What area of the colon does UC affect?
The rectum first and then extends proximal to involve more of the colon
What proportion of those with UC have left sided colitis?
30%
What proportion of those with UC have proctitis?
50%
1/3rd of these will go on to develop proximal disease
What are the characteristics of proctitis?
Frequent passage of blood and mucus
Urgency
Tenesmus
Few constitutional symptoms
Stool may be solid but pt are inconvenienced with frequency
What are the characteristics of left-sided or extensive UC?
Blood diarrhoea up to 10-20 liquid stools a day (also occurs at night)
Urgency and incontinence that is severely disabling for the pt
What is toxic megacolon?
a serious complication associated with acute severe colitis characterised by extreme inflammation and distension of the colon
It’s a medical emergency and pt must be admitted. it puts you at risk for infection throughout the body, shock, and dehydration.
It is a particularly dangerous stage of advanced disease, with impending perforation and a high mortality (15–25%). Urgent surgery is required in all patients in whom toxic dilation has not resolved within 48 hours, with intensive therapy as above.
What would you see on plain abdominal X-ray of toxic megacolon?
Dilated, thin-walled colon with a diameter >6cm
Gas’s filled ands contains mucosal islands
What examination signs can indicated UC?
Abdomen may be slightly distended or tender to palpate
Tachycardia and pyrexia are signs of severe colitis
Anus is usually normal
Rectal examination will reveal presence of blood
Pallor, clubbing, aphthous mouth ulcers
Signs of malnutrition or malabsorption - weight loss, faltering growth, delayed puberty
Eye, skin or joint signs (extra-intestinal manifestations)
What would be seen on sigmoidoscopy in UC/
usually abnormal, showing an inflamed, bleeding, friable mucosa.
What are the risk factors for UC?
FHx
No appendicectomy before adulthood
NSAIDs
Not smoking
What are the complications of UC?
Psychosocial impact
Toxic megacolon
Bowel obstruction
Bowel perforation
Massive haemorrhage
Intestinal strictures
Fistulas
Anaemia
Malnutrition, faltering growth and delayed pubertal development in children
Growth failure in children
Colorectal cancer (more likely than with Crohn’s disease)
Pouchitis
What are the symptoms of toxic megacolon?
Escalating abdo pain
Systemic symptoms - fever, tachycardia, dehydration
What can precipitate toxic megacolon?
Infection
Hypokalaemia
Hypomagnesaemia
Medical bowel preparation
Use of anti-diarrhoea drugs
What are the extra-intestinal manifestations of UC?
Pauci-articular arthritis, Axial arthritis, Polyarticular arthritis
Erythema nodosum, pyoderma gangrenosum
Aphthous mouth ulcers
Episcleritis, uveitis
Metabolic bone disease (osteopenia, osteomalacia, osteoporosis)
Hepatobiliary conditions
VTE
What macroscopic changes can be seen in UC?
Evidence of continuous inflammation that extends proximal along the colon
Surface of mucosa appeared reddened and inflamed
Mucosa is friable to touch
May be evidence of inflammatory polyps
What microscopic changes can be seen in UC?
Crypt abscesses
Goblet cell depletion
Inflammatory infiltrate in lamina propria, which is largely neutrophilic
What blood work investigations should be done for UC?
FBC (may see IDA due to blood loss and raised platelet count due to inflammation and raised WCC)
CRP and ESR
Us&Es (assess for electrolyte disturbance and signs of dehydration)
LFTs and albumin (low serum albumin in severe disease)
TFT (exclude hyperthyroidism)
Ferritin
B12 and folate
Vit D levels
Coeliac serology
P-ANCA may be positive
What stool tests should be done for UC?
Stool micscopy and culture, include C.diff toxin (exclude infective gastroenteritis or pseudo membranous colitis)
Stool microscopy to exclude amoebiasis in pt with relevant travel history
Faecal calprotectin and lactoferrin will be elevated
What imaging should be done for UC?
Endoscopy with mucosal biopsy - gold standard for diagnosis
(Full colonoscopy should not be performed in severe attacks for fear of perforation)
Plain abdominal x-ray to exclude colonic dilation
On plain abdominal x-ray when is dilation said to be present in…
Small bowel?
Large bowel?
Caecum?
Small bowl - diameter >3cm
Large bowel - diameter >6cm
Caecum - diameter >9cm
What classification is used for ulcerative colitis?
Truelove and Witt’s classification
When considering Truelove and Witt’s classification, what is considered mild UC?
<4 bowel movements a day
No/small amount of blood in stool
No pyrexia, tachycardia or anaemia
ESR <30
When considering Truelove and Witt’s classification, what is considered moderate UC?
4-6 bowel movements a day
Moderate-severe blood in stool
Intermediate pyrexia, tachycardia, anaemia and ESR
When considering Truelove and Witt’s classification, what is considered severe UC?
> 6 bowel movements a day
Visible blood in stool
Pyrexia and tachycardia
Anaemia <105g/L
ESR >30
What follow up do pt with UC need?
Colorectal cancer surveillance after 10 years of diagnosis (excluding proctitis alone)
Children and young people must have their growth and pubertal development monitored regularly
Once on medication monitor serum ferritin, B12, folate, calcium, Vit D
Assess for clinical features suggesting a flare-up = check BMI for weight loss and serum inflammatory markers
Ensure pt has had appropriate vaccinations
What specialist drug treatment is given to induce remission in mild-moderately active UC? Does it also maintain remission?
Aminosalicylates (5-ASA) e.g. mesalazine and sulfasalazine (THESE ARE FIRST LINE! Second line prednisolone)
Also effective at maintaining remission
Given topically if mild to moderate and topically+orally if extensive UC
If proctitis they can be treated with 5-ASA suppositories alone
How are Aminosalicylates often given in UC?
Topically as a suppository or enemies
Orally if remission is not achieved within 4 weeks
When are corticosteroids offered for inducing remission of UC?
Patients who fail to respond to maximum dose of 5-ASA agents, or those with moderate-to-severe UC
Add these onto 5-ASA
What can be used to induce remission in UC if there is inadequate response to oral corticosteroids after 2-4 weeks?
Adding a calcineurin inhibitor such as tacrolimus or Ciclosporin
Note this is on top of the corticosteroids
What can be used to maintain remission of UC if there are 2 or more inflammatory exacerbations in a 12 months period that require treatment with oral corticosteroids, or if remission cannot be maintained by aminosalicylates?
Immunosuppressive drugs
Thiopurines or methotrexate (second line)
What drugs can be used for inducing remission in people with severe active UC which has not responded to conventional therapy, or where conventional therapy is not tolerated?
Biological therapy - anti-TNF a plea monoclonal antibody agents e.g. infliximab (IV), adalimumab (subcutaneous) and golimumab (subcutaneous)
Note these drugs are also effective at maintaining remission
What may be used for inducing remission of UC in children?
Specialist enteral nutritional supplementation
What are the clinical features of acute severe disease/flare up of UC/
Severe diarrhoea, nocturnal diarrhoea, or bloody diarrhoea (more than 6–8 stools a day).
Fever, dehydration, tachycardia, or hypotension.
Severe abdominal pain or suspected intestinal obstruction.
Signs of malnutrition with a body mass index (BMI) less than 18.5 kg/m2, or unintended sudden weight loss.
Raised inflammatory markers and/or anaemia.
Persistent symptoms despite optimal management in primary care.
How should you manage a flare up of UC?
Consider whether symptoms could be due to an alternative condition e.g. c.diff infection
Check persons adherence to current drug treatment regime
Consider arranging urgent specialist gastroenterology review appointment or seeking specialist advise - they may start a short course of oral corticosteroids (dont prescribes NSAIDs)
Consider arranging a referral to a dietitian if there are signs of unintended weight loss or malnutrition.
If there are recurrent flares of disease activity, seek specialist advice regarding whether the person’s maintenance treatment regimen needs to be changed to improve disease control, or whether surgery may be needed.
Is surgery recommended for UC? Whats the indication?
The treatment of UC remains primarily medical but surgery is still used occasionally because its curative and eliminates the long term risk of cancer
Indications are severe colitis that fails to respond to medical therapy, and chronic active therapy-refractory disease
Whats the surgery of choice for UC?
Subtotal colectomy with end ileostomy and preservation of the rectum
What is pouchitis?
inflammation of the pouch mucosa with clinical symptoms of diarrhoea, bleeding, fever and, at times, exacerbation of extracolonic manifestations
(The pouch is what replaces the rectum)
What is J-pouch surgery?
A proctocolectomy with ileal pouch-anal anastomosis
- constructing an ileal pouch anal-anastomosis (IPAA) or j-pouch. The surgeon will remove your colon and rectum and use the end of your small intestine, known as the ileum, to form an internal pouch, which is commonly shaped like a J.
It’s very technical difficult and there is a risk of pelvic nerve damage
What are the risk factors for the development of pouchitis?
presence of extraintestinal manifestations, primary sclerosing cholangitis, non-smoking, and postoperative non-steroidal anti-inflammatory drug usage.
Whats the mainstay of treatment for pouchitis?
Antibiotics (metronidazole with or without ciprofloxacin)
Steroids may be needed if this is not satisfactory
What can be used to prevent the onset of pouchitis and maintain remission in patients with antibiotic treated pouchitis?
Probiotic VSL#3
What is microscopic colitis?
inflammation of the colon that causes persistent or fluctuating watery Diarrhoea
Macroscopic features on colonoscopy are normal but histopathological findings on biopsy are abnormal
It’s another type of IBD but, unlike the others, cannot increase your colon cancer risk
Outline the use of treatment in Crohn’s vs UC?
UC is potentially curable with colectomy
Crohn’s disease surgery is only used for localised severe disease but this is not curative
Why is mesalazine preferred over sulphasalazine for treating UC?
Because mesalazine is one of the 2 components of sulphasalazine, the other being sulphapyridine which is responsible for most side effects = mesalazine has less side effects
Whats the moa of mesalazine?
It has a topical anti-inflammatory effect on colonic epithelial cells and reduces inflammation through a variety of anti-inflammatory processes
How does IBD affect men and women differently?
Crohn’s affects them equally
UC affects more women then men
What barium enema x-ray features are seen in acute severe colitis?
Thumb printing in the transverse colon
Leadpipe appearance of descending and sigmoid colon - loss of haustral folds
What are the SE of anti-TNF agents?
Infections - particularly risk of re-activating latent infections e.g. TB
Malignancies - small risk but particularly lymphoma
Congestive Heart Failure
Drug-Induced Lupus
Demyelinating Disorders (MS-like illness)
Skin Reactions
What do thumbprinting and lead pipe colon show?
The thumbprinting represents wall oedema and likely represents more acute (active) disease
lead pipe appearance more distally representing chronic disease
What crohns classification tools do we use?
Crohn’s disease activity index (tells you if its in remission, active, severe active disease) - complex
Harvey-Bradshaw index (tells you if in remission, moderately active or severe active disease) - simpler to use
What are the adverse effects of sulphonamides?
Nausea
Rashes
Blood disorders e.g. agranulocytosis, aplastic anaemia, haemolytic anaemia
Stevens-Johnson syndrome - rare but serious
Whats the most commonly affect site of the common site of the colon affected by UC/
Recto-sigmoid area
What area of the colon is most affected in Crohn’s disease?
Ileocaecal area
What investigations do we do for IBD/
FBC
LFTS and albumin
ESR and CRP
Blood cultures
Microscopy culture sensitivity of stool
endoscopy and colonoscopy
Biopsy for UC - crypt abscess, atrophy, mucin depletion, inflammatory signs
Radiology for Crohn’s - essential for staging. Traditional barium is used
Why does crohns cause vit B12 deficiency?
Because crohns affects terminal ileum where B12 should be absorbed
Why can Crohn’s disease cause gallstones?
Because bile salts are reabsorbed in the terminal ileum and this can be affected in Crohn’s. No bile salts causes cholesterol stones to be more likely to be formed
Is IBD curative?
There are no existing cures for Crohn’s disease, whereas a colectomy (removal of the colon or large bowel) may be considered “curative” and induce remission in ulcerative colitis.
Whats the difference in aims with surgery for UC and crohns?
Crohn’s you want to leave as much bowel as possible as it can come back because of the skip lesions
In UC you want to re,ove the entire section of the bowel
Why should you do a chest x-ray in ulcerative colitis?
Because they are at increased risk of perforation - air will be under the right hemi-diaphragm
How do you manage acute severe colitis?
ABC and resuscitation with IV fluids
Hydrocortisone to control some of the systemic and local inflammation
Thromboprophylaxis
Monitor vitals, bloods, stool chart and Abdominal XRay to look for presence of toxic megacolon
What do you use for topical therapy of proctitis or more proximal disease?
Proctitis - suppositories
Proximal disease - enemas or foams
What are examples of corticosteroids used for IBD
Prednisolone
Dexamethasone
Budesonide
IV hydrocortisone
What monitoring is required for corticosteroid use for IBD?
Assess for osteoporosis, Cushin good features, hyperglycaemia, cataracts and glaucoma
What are the significant SE of corticosteroids?
Systemic infections
Gastritis
Diabetes
Heart failure
Psychiatric effects
Sleep disturbance
Osteoporosis
Growth suppression in children
What are examples of aminosalicylates?
Masala one and sulfasalazine
What monitoring is required for mesalazine?
Renal function should be monitored before starting an oral aminosalicylate, at 3 months of treatment, and then annually during treatment.
What monitoring is required for sulfasalazine?
Renal function should be monitored before starting an oral aminosalicylate, at 3 months of treatment, and then annually during treatment
Close monitoring of full blood counts (including differential white cell count and platelet count) is necessary initially, and at monthly intervals during the first 3 months.
LFTs should be performed at monthly intervals for first 3 months.
What are side efefcts of aminosalicylates?
Worsens headache
Arthralgia; cough; diarrhoea; dizziness; fever; gastrointestinal discomfort; leucopenia; nausea; skin reactions; vomiting
What are examples of immunosuppressants used in IBD?
Azathioprine
Mercaptopurine
Methotrexate
What monitoring has to be done for immunosuppressant use in IBD?
Once stable FBC and LFTs every 3 months
U&Es every 6 months (if methotrexate then every 3 months)
What are the significant side effects of immunosuppressants used in IBD?
Increased susceptibility to sunburn, risk of cervical abnormalities and susceptibility to infections
Potential increased risk of lymphoma
What are examples of biological agents used in IBD?
Infliximab
Adalimumab
Golimumab
Vedolizumab
Ustekinumab
What are significant side efefcts of biological agents used in IBD?
Injection site skin reactions
Increased susceptibility to infections e.g. TB
What are 2 serious drug interactions with azathioprine?
Allopurinol and febuxostat - slow elimination of azathoppirne by inhibiting xanthine oxidase
What is 6-mercaptopurine?
When azathoprine is non enzymatically neutrophil attacked by sulfhydryl-containing compounds e.g. glutathione it produces 6-MP
Whats the moa of infliximab?
Neutralises biological activity of TNF-alpha by binding to its receptors
It can also stimulate apoptosis of activated lymphocytes in the gut mucosa
Where are strictures likely to develop in crohns?
Terminal ileum and at surgical anastamosis
What can endoscopic balloon dilation be used for?
Small bowel crohns and anastomotic structures of <5cm that are endoscopically accessible with no associated abscess or fistula
When should a structureplasty be considered in crohns?
When there are multiple strictures present or concern about preservation of bowel length
Which patients should be given VTE prophylaxis?
All regardless of rectal bleeding!
Whats the risk of colonic cancer if you have IBD?
10% for pancolitis after 20 years
What is a spout on a stoma?
A spout is used for ileostomies to prevent skin irritation from the small bowel contents produced by the stoma.
Where on the abdomen do you tend to find colostomies vs ileostomies?
Colostomies - LIF
Ileostomies - RIF
What does 1 lumen on the stoma mean?
It’s likely an end ileostomy/colostomy rather than a loop ileostomy/colostomy
What is the effluent from colostomies?
Solid and semisolid faeces
What is the effluent from ileostomies?
Liquid/mushy small bowel content
What is a gastrostomy?
Gastrostomy is the creation of an artificial external opening into the stomach for nutritional support or gastric decompression.
What is a jejunostomy?
the surgical creation of an opening (stoma) through the skin at the front of the abdomen and the wall of the jejunum
What is an ileostomy?
a stoma constructed by bringing the end or loop of small intestine out onto the surface of the skin, or the surgical procedure which creates this opening
What is a colostomy?
an operation to divert 1 end of the colon (part of the bowel) through an opening in the tummy. The opening is called a stoma
What is a caecostomy?
An operation involving bringing the caecum through the abdominal wall
What is a mucous fistula?
attaches a disconnected part of your intestine to a surgically created small opening in the skin on your belly (stoma). This connection helps people with certain bowel diseases pass mucous (intestinal secretions) out of the stoma instead of the anus
What are the pros of a stoma?
Urgency is reduced
Reduces pain
Quick and easy to change
Little to no diet restrictions
No smell
What is colostomy irrigation?
a way to remove stool without wearing a colostomy bag all the time. You use the stoma to wash out the colon with water (like an enema). You perform this procedure at the same time every day, or every other day, depending on your needs.
What are the advantages of colostomy irrigation?
You choose when you want to perform irrigation
You do not have to wear a colostomy appliance but may have to wear a small cap
You should be able to enjoy a more varied diet
Less flatulence
What are the disadvantages of colostomy irrigation?
45-60 minutes to complete
Has to be done every day
For best results it should be carried out at the same time every day
It’s not suitable for those with crohns, diverticulitis, radio/chemotherapy
What diet is needed with a stoma?
Just for the first few weeks you should have a low fibre diet - high fibre can increase the size of your stools and temporarily block your bowels
Why dont stoma’s smell?
All modern appliances have air filters with charcoal in them, which neutralises the smell.
What does PEG tube stand for?
Percutaneous endoscopic gastrostomy -
the placement of a feeding tube through the skin and the stomach wall done using endoscopy
Whats the purpose of loop ileostomy/colostomy?
usually intended to be temporary and can be reversed during an operation at a later date.
Typically to protect a surgical join in the bowel
What is a J-pouch surgery?
An ileoanal anastomosis surgery
Ileal pouch-anal anastomosis surgery
Why is a J pouch done?
Often for UC and inherited conditions that carry a high risk of colorectal cancer
What is done during J-pouch surgery
Laparoscopically they remove the entire colony dn rectum but preserver the muscular sphincter and anus
They construct a pouch shaped like a J from the end of the ileum and attach it to the anus
They create a temporary ileostomy but after about 3 months of healing they close this to allow you to pass stool normally
What are the issues with J-pouch surgery?
People >45 tend to experience more incontinence and have to go to the bathroom more frequently at night
Most people have about 6 bowel movements a day and 1 at night
Pouchitis is common
Eating restrictions
How are perianal abscesses treated?
Incision and drainage
What are the main differences in symptoms of Crohn’s disease vs ulcerative colitis?
Crohn’s - diarrhoea usually non-bloody. Weight loss more prominent. Upper GI symptoms. Perianal disease. Abdominal mass palpable in RIF
UC - bloody diarrhoea more common. Abdominal pain in left lower quadrant. Tenesmus
What is the investigation of choice for suspected perianal fistulae in patients with Crohn’s?
MRI pelvis
What are the different pathologies behind crohns and UC?
Crohs - Th17 and IL23 - immune reaction inflammation = destruction transmural
UC - Th2
Where are the typical locations of pain in Crohn’s and UC?
Crohns -RLQ
UC - LLQ
What are granulomas?
Small areas of chronic inflammation characterised by collections of macrophages that may damage organ tissue
They are typically accompanied by CD4+ helper T cells
In which situations may granulomas form?
when there is either a continuous T-cell response
or
when the body attempts to contain a pathogen it is unable to eliminate.
What are the 2 categories of granulomas?
Caseating and noncaseating
What are the characteristics of caseating granulomas?
They have a central region of necrosis
They classically appear cheese-like upon biopsy
Typically form in the lungs in response to TB and fungal infections
What are the characteristics of noncaseating granulomas?
Dont have a central region of necrosis
Occur more commonly
May form in response to contact with foreign material, sarcoidosis, vasculitis and Crohn’s disease
