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!)
