IBD/other non-malignant/non anorectal Flashcards
What blood tests can help in the diagnosis of Crohns and UC?
ASCA +ve in 35-50% of Crohns pts cf <1% UC.
p-ANCA often raised in UC (sens 55%, spec 90%); if raised in Crohns, only with colitis
What is faecal calprotectin?
A protein with antimicrobial properties released by squamous cells in response to inflammation
What is the aetiology of Crohn’s disease?
Interplay between environmental and genetic factors; probably results from a genetic predisposition to an abnormal interaction between immune system & environmental factors, espec gut microbiota. Specific cause of exaggerated inflam response at mucosal level unclear. Number of potential causes proposed - most likely being infectious, immunologic & genetic; other possibilities environmental & dietary factors, smoking, psychological factors
How is Crohn’s disease classified?
Montreal classification
- Age at diagnosis: A1 <16, A2 17-40, A3 >40
- Location: L1 ileal, L2 colonic, L3 ileocolonic, L4 isolated upper disease (modifier that can add to L1-3 when present)
- Behaviour: B1 non-stricturing and non-penetrating, B2 stricturing, B3 penetrating, P = perianal disease modifier
By phenotype: inflammatory, fibrostenotic, fistulising
Crohn disease activity index (CDAI) – to quantitate symptoms
- 8 clinical & lab variables, incl no of BM/day, presence of abdo pain, haematocrit, weight loss, 7 day symptom diary
- score <150 = clinical remission; score >450 = severe disease
Harvey-Bradshaw index
What are the operative options for UC?
- Total abdominal colectomy and end ileostomy (acute operation)
- Proctocolectomy & end ileostomy (pt preference, low rectal ca, poor sphincter function)
- Proctocolectomy + IPAA (stapled better QOL but higher risk dysplasia/malignancy in retained mucosa (v rare) cf handsewn)
- Proctocolectomy + continent ileostomy
- Total abdominal colectomy + IRA (only if rectum minimally inflamed, no rectal dysplasia, intact sphincter mechanism, willing to adhere to strict f/u - risk of rectal ca 20% by 30yrs)
What are the factors which increase the risk of CRC in IBD?
3-5x increased risk colon ca, tend to get at younger age and higher mortality
Factors which increase risk:
- disease duration + extent
- severity of inflammation
- PSC
- FHx of CRC
- Presence of dysplasia
What are the two biologics used in IBD in NZ?
Anti-TNF alpha antibody
Infliximab (Remicade) = mouse-human chimeric monoclonal antibody, IV infusion 8wkly
Adalimumab (Humira) = fully human monoclonal antibody, SC injection fortnightly
What is ulcerative colitis?
An idiopathic and relapsing inflammatory bowel disease involving the lamina propria of the rectum and variable extent of the proximal colon - characterised by remissions & exacerbations. The inflammation spares the anus and is continuous to its proximal extent. Can be associated with extra-intestinal manifestations.
What is Crohn’s disease
A chronic, transmural inflammatory process that can affect GIT anywhere from mouth to anus with skip lesions & can be associated with extraintestinal manifestations.
What are the causes of colitis?
Infectious
Bacteria
- Campylobacter – spiral microaerophilic gram +ve rod
- C diff – anaerobic, spore forming, gram +ve rod
- Salmonella – gram –ve facultatively anerobic rod
- Shigella – gram –ve facultative anaerobic rod
- Enterotoxic E coli – gram –ve facultative anaerobic rod
- Yersinea – gram –ve coccobacillus
Parasitic
- Entaemoeba histolytica
- Cryptosporidium
Viral
- CMV
Inflammatory
- UC, Crohn’s
Ischaemic
Microscopic colitis
Behcet’s
NSAIDs
How is colitis severity classified
Clinical: Truelove and Witt’s criteria (she hasn’t even finished pooping)
- Severe = ≥6 bloody stools a day and one of Hb <105, ESR/CRP >30, Febrile >37.8, Pulse >90
- Moderate =
- Mild =
Endoscopically: Mayo criteria
What is toxic megacolon?
Dilation of the colon in the setting of systemic toxicity, secondary to any infectious or inflammatory disease of the colon
Pathogenesis
- as mucosa sloughs, endotoxins within bowel lumen are absorbed –> septic state characterised by leukocytosis, tachycardia, fever +/- haemodynamic instability
- colonic inflammation increases production of inducible nitric oxide synthase by macrophages & SM cells - NO inhibits SM tone which contributes to colonic dilation
- while only mucosa is inflamed in typical UC, SM layer is inflamed & paralysed in toxic megacolon which can contribute to colonic dilatation
- inconclusive whether myenteric plexus of colon is damaged in toxic megacolon
Diagnosis
- Suspect if distension and diarrhea
- Criteria:
- Transverse colon diameter >6cm AND
- Plus any 3 of following:
- Fever >38, tachycardia >120, WC >10.5, anaemia <60% of normal
- Plus any 1 of the following:
- Dehydration, electrolyte imbalances, altered mental state, hypotension
How do you decide if IV steroids are working in acute severe colitis?
Travis criteria – on day 3 if stool frequency >8 or stool frequency 3-8 and CRP >45, 85% require colectomy (but from a time where corticosteroids were only thing in toolbox from medical point of view)
What is the aetiology of ischaemic colitis
- Physiological – low-flow states
- Eg hypotension (incl sepsis), hypovolaemia, haemorrhage, cardiovascular, heart failure, atherosclerosis)
- Hypercoagulable
- Factor V Leiden, Protein C&S deficiency, Prothrombin G2010A mutation, antiphospholipid syndrome (Lupus anticoagulant), Antithrombin III deficiency, PCV, DIC, HITT
- Autoimmune disease
- SLE
- Tobacco (acquired)
- Drugs
- Vasopressors, OCPs, diuretics, antiarrhythics, antihypotensives
- Immunomodulatory drugs eg anti-TNF-a inhibitors can affect thrombogenesis
- Illicit drugs eg cocaine & meth – thru vasoconstriction, hypercoagulation, direct endothelial injury
- Surgery/procedural
- Cardiac, aortic
- Pts undergoing aortic reconstructive surgery or abdo surgery in which IMA is ligated if collateral circulation not sufficient
What are the two well-described collateral networks that aid in preventing colonic ischaemia?
- Marginal artery of Drummond – runs parallel & close to mesenteric margin of colon from caecocolic junction to rectosigmoid junction – colon can receive collateral blood supply through this artery when one of larger arteries is obstructed
- Important when resecting a section of colon to preserve this since only vasa recta are located between it and colon
- When compromised, ischaemia of that section of colon may result
- Arc of Riolan (meandering mesenteric artery) = found in prox region of large arteries – traverses close to mesenteric root, connects SMA or middle colic to IMA or left colic
- Can have critical role in situations of SMA or IMA occlusion
- Presence of large arc of Riolan commonly indicates obstruction of one of the major mesenteric arteries
What are the two watershed areas of the colon?
- Found at edge of region supplied by the SMA & IMA – these zones are frequently dependent upon collateral circulation
- Splenic flexure (Griffiths point) – up to 50% lack a marginal artery in region where SMA & IMA circulations meet
- Rectosigmoid junction (Sudeck’s point) – receives blood supply from superior haemorrhoidal artery & distal sigmoid branches, both terminal branches of IMA & prone to atherosclerotic changes
- Right colon, though not classically considered a watershed area, is also vulnerable to ischaemia from embolic occlusion bc ileocolic is terminal branch of SMA; so R colon also particularly prone to low-flow conditions eg heart failure, haemorrhage, sepsis
How is ischaemic colitis classified and managed?
- Mild disease: segmental, not isolated to right colon, and lacking poor prognostic factors observed in moderate disease
- Moderate disease includes any 3 of the following:
- Tachycardia
- Abdo pain w/o rectal bleeding
- Hypotension
- Male sex
- BUN >20mg/dL
- Na <136
- WCC >15
- Hb <12
- Colonoscopically identified ulceration
- Severe disease: >3 of moderate disease criteria or peritoneal signs, pneumatosis or portal venous gas w CT imaging, gangrene on colonoscopy, and pancolonic or isolated right colon ischaemia on CT or endoscopy
- mild and moderate: treat supportively + treat underlying cause (abx can be considered to decrease sequelae of bacterial translocation but lack of robust data to support this)
- full thickness necrosis and gangrene, peritonitis, pneumoperitoneum or haemodynamic instability: immediate surgery
- in contrast to mesenteric ischaemia of small intestine, usually no indication for revascularising the large bowel in primary colonic ischaemia, which is not generally related to large artery obstruction
- (only need CTA if acute mesenteric ischaemia suspected w pain out of proportion and lack of haematochezia, or if isolated right sided)
What are the absolute indications for colectomy in acute severe colitis?
Toxic megacolon
Perforation
Haemorrhage
Multiorgan dysfunction
What are the indications for colectomy in colitis in general?
- Failure to respond to maximal medical therapy
- Pts w severe disease – multiple BMs, poor nutritional status, failure to thrive, poor QOL
- Pts w acute severe colitis
- Perforation
- Significant GI bleeding
- Toxic megacolon
- Drug intolerability
- Growth impediment in children
- Dysplasia or malignancy
- For attempted improvement of some extra-intestinal manifestations refractory to medical treatment
Outline the principles of medical management of IBD
- Short term: Induce remission
- Corticosteroids (UC and Crohn’s)
- 5-Aminosalicylates (UC only)
- Long term: maintain remission
- 5-aminosalicylates (Pentasa/Asacol) (minor benefit in crohn’s colitis only)
- thiopurines (azathioprine)
- methotrexate/cyclosporine
- biologics (infliximab/adalimumab)
- symptomatic response alone not predictive of clinical course; now want to see
- symptomatic remission and normalization of CRP
- decrease faecal calprotectin to acceptable range, normal growth in children
- endoscopic healing, normalized QOL
- consider histologic healing also
Outline the medical treatment of UC
Disease severity at presentation
- Mild – induction w aminosalicylate, maintenance w aminosalicylate
- Moderate – induction w corticosteroid, maintenance w aminosalicylate & thiopurine (MTX)
- Severe – induction w anti-TNF, cyclosporine, maintenance w anti-TNF, thiopurine, vedolizumab
- Very severe at presentation – colectomy
- NB for proctitis and mild-mod distal colitis, topical mesalamine supps/enemas = better than oral, +/- add topical steroids +/- add oral mesalamine
- For mild-mod extensive colitis, give oral asacol + topical therapy too
Outline surveillance for colorectal cancer in IBD
- Starting time for surveillance in at risk pts
- UC beyond sigmoid OR CD >1/3 of colon or complicated anorectal disease = no later than 8yrs after onset sx
- If PSC detected = at time of dx of PSC
- If strong FHx of CRC = before 8yr after onset of sx
- Optimal surveillance intervals
- Group 1 = any high risk feature
- Chronically active UC
- PSC
- CRC in FDR at <50y age
- Stricture, multiple inflammatory polyps or shortened colon
- Previous dysplasia
- = 1yrly colonoscopy
- Group 2:
- Quiescent UC w/o high risk features
- = 3yrly colonoscopy
- Group 3:
- UC w/o high risk features when 2 previous colonoscopies are macroscopically inactive and histologically negative for dysplasia
- = 5yrly colonoscopy
- Group 1 = any high risk feature
What are the extraintestinal manifestations in Crohn’s disease?
- Related to disease activity
- Aphthous ulceration (10%)
- Erythema nodosum (5-10%) – see UC for more details
- Pyoderma gangrenosum (0.5%) – see UC for more details
- Acute arthropathy (6-12%)
- Eye complications (conjunctivitis etc) (3-10%)
- Amyloidosis (1%)
- Unrelated to disease activity
- Sacroiliitis (often minimal sx) (10-15%)
- Ankylosing spondylitis (1-2%)
- PSC (rare)
- Chronic active hepatitis (2-3%)
- Cirrhosis (2-3%)
- Gallstones (15-30%)
- Renal calculi (5-10%)
What are the extracolonic manifestations of UC?
20% of those w UC will get; slightly less than Crohn’s
- those that respond to colectomy: peripheral arthropathy, erythema nodosum, episcleritis
- sometimes: pyoderma gangrenosum
- don’t respond: axial arthropathy, PSC, uveitis, scleritis
D. MOTH
Derm
- erythema nodosum (related to bowel activity)
- 10-20% of UC, can precede bowel stuff
- pyoderma gangrenosum (sometimes related)
- 10-10%
- plaques or pustules that break down & form painful ulcerations w undermined borders & necrotic centers
- legs most common but can happen anywhere incl peristomally
- get worse w surgery - non op tx incl intralesional steroids, topica tacrolimus, systemic biologics
MSK (most common)
- asymmetrical peripheral arthropathy involving small & large joints (related to disease activity)
- ank spond
- asymptomatic sacroileitis (both not related)
Ophthal
- episcleritis (responds) and uveitis (doesn’t) most common
- also scleritis, conjunctivitis
Thromboembolic
- VTE risk 3x higher
- rare = cerebral venous & dural sinus thrombosis
- hypercoagulable state
HPB
- PSC (not related)
- idiopathic, chronic & progressive disorder - stricturing, inflam, fibrosis of intra and extrahepatic bile ducts
- 5% of pts w UC get PSC; >5% of pts w PSC have UC
- cholangiocarcinoma rare assoc w UC & PSC
What is the medical management of Crohn’s
- Concept = induce remission then maintain it
- Most effective agent for inducing remission = a corticosteroid, and 2nd-line agents = TNF inhibitors, infliximab or adalimumab
- For moderate to severe disease, steroids are commenced & at the same time immunomodulators (usually azathioprine)
- After some weeks or months, when therapeutic benefit of immunosuppression commences, steroids can be removed
- Aminosalicylates (sulfasalazine & 5-ASA) have modest efficacy for mild to moderate Crohn’s colitis
INDUCTION OF REMISSION:
Mild to moderate disease
- Prednisone 20-40mg daily for 2-3 weeks then tapering
- Ileal and/or right colon: budesonide 9mg per day
- Crohn’s colitis: appropriate salicylate compound (oral and/or enema)
- Perianal disease: metronidazole 400mg tds or Cipro 500mg BD
Severe disease
- IV hydrocortisone 400mg daily in divided doses
- Infliximab, adalimumab or other biological (second-line)
MAINTENANCE OF REMISSION
- Azathioprine, 6-mercaptopurine, methotrexate, budesonide 6mg per day (ileal and/or right colon), infliximab or adalimumab
Differential diagnoses for terminal ileitis
- Infection: TB, Yersinia, Salmonella, CMV, neutropenic enterocolitis
- NSAID enteropathy
- Malignancy: lymphoma, carcinoid
- Lymphoid nodular hyperplasia
- Crohn’s
- UC with backwash ileitis
Crohns in pregnancy
in absence of active disease, outcome of pregnancy = that of matched controls
w active disease at conception, in spont abortions & premature delivery, and a 50% chance of relapsing disease during pregnancy
risk of relapse only 20-25% if disease inactive at conception – ie avoid conception during acute phase of disease
pregnancy probably doesn’t affect long-term course of disease
How can diarrhoea be classified?
- Acute - 14 days duration or less
- Persistent - Between 14-30 days duration
- Chronic - More than 30 days duration
- Secretory:
- S. aureus, Cholera, VIPoma, Carcinoid syndrome, Adenomas
- Exudative:
- IBD, Colorectal cancer, Campylobacter
- Osmotic:
- Lactose intolerance
- Laxatives
- Surgical changes
- Abnormal motility:
- Irritable bowel syndrome
- Thyrotoxicosis
How are the different phenotypes of Crohn’s classified?
The Montreal (nee Vienna) classification system. Classifying phenotype is relevant for studying the outcome of therapy, medical or surgical.
p is added if perianal disease is present.