Crohn's disease

Crohn's disease is a chronic transmural inflammatory disease of the GIT

History

• First documented by Morgagni in 1761
• Landmark paper by Crohn et al in 1932 that truly defined the disease

Epidemiology

• Most common in Western countries
• Bimodal onset - mostly 15-25yo, with a second smaller peak around 60yo

Risk factors

• Previous tonsillectomy/appendicectomy
• Urban living
• Equal gender balance
• Smoking (OR 2)
• Born during Spring
• Live in higher latitudes
• More common in Western society
  • Those migrating to Western countries also get CD at same rate as those born in Western countries
• Family history (OR 30 in siblings, 14-15 in first-degree relatives; 20-50% concordance in monozygotic twins and 4% concordance in dizygotic twins)
• Certain intestinal flora and epigenetic changes

Protective factors

• Childhood vegetable garden

Aetiology is unknown, but the following causes have been proposed. The true aetiology is likely a combination.

• Infectious
  • Mycobacterial infections are plausibly causative, particularly Mycobacterium paratuberculosis and enteroadherent E. coli
  • PCR studies have confirmed the presence of mycobacteria in patients with CD
  • Transplantation of tissue from CD patients has resulted in ileitis, but antimicrobial therapy against mycobacteria has not cured established CD
• Immunologic
  • Humoral and cell-mediated immune reactions directed against intestinal cells in CD suggest an autoimmune phenomenon
  • Especially IL-1, IL-2, IL-8 and TNF-a
  • Remains controversial - may reflect effect rather than cause
• Genetic
  • >200 alleles associated with CD, most frequently NOD2, MHC, and MST1 3p21
  • NOD2 is associated with decreased expression of antimicrobial peptides by Paneth cells (homozygosity confers a 17-40x risk)
  • Family history is the strongest single risk factor
  • Twin genetic comparisons have suggested that simple Mendelian inheritance does not account for occurrence
• Other factors thought to be possible but less important:
  • Environmental
    • As countries adopt a more Western lifestyle, the incidence of CD rises
    • Dysbiosis - decrease in intraluminal Bacteroides and Firmicutes and increase in Gammaproteobacteria and Actinobacteria are associated with higher risk
  • Dietary
    • Decreased fibre
    • Increased fat
  • Smoking
  • Psychosocial
  • Medications
    • COCP, aspirin, NSAIDs

Pathophysiology

• Development
  • Genetically predisposed individual
  • Environmental triggers and microbiome alterations
  • Disordered immune responses - abnormally heightened
  • Transmural inflammation throughout GIT
  • Inflammatory stricturing and penetrating phenotypes
• Can involve any part of the GIT from mouth to anus, but most commonly affects small bowel and colon. Location of disease in influenced by genetics
  • 30% present with small bowel disease alone
  • 15% with large bowel alone
  • Perianal involvement occurs in 30%, especially those with colonic involvement
• Discontinuous and segmental disease
• Rectal sparing is characteristic of CD - helps distinguish from UC

Histological findings

• • Mucosal and submucosal oedema
  • Chronic inflammatory infiltrate in the mucosa and submucosa, extending transmurally - characterised by extensive oedema, hyperaemia, lymphangiectasia, intense infiltration of mononuclear cells, and lymphoid hyperplasia
  • Ulceration
  • Normal number of goblet cells, whereas depleted goblet cells are seen in UC
  • Preserved glandular architecture
  • Crypt abscesses can found in either UC or CD, but more common in UC
  • Characteristic lesions are non-caseating granulomas with Langerhans giant cells
    • Found later in the course
    • May appear in wall of bowel or regional lymph noes in 60-70% of patients
  • Intra-lymphatic granulomas
  • Granulomatous vasculitis

Presentation

• Classical presentation:
  • Insidious onset
  • Alternating symptomatic periods with abdominal pain and diarrhoea interspersed with asymptomatic periods. With time, the symptomatic periods become more severe, more frequent, and longer lasting
• Symptoms:
  • Chronic diarrhoea - most common symptom
    • Stools rarely contain blood, mucus or pus (in contrast to UC)
    • Fewer daily bowel motions than UC
  • Abdo pain - intermittent and colicky, commonly lower abdomen, and sometimes localised to RLQ
  • Low-grade fever (~30%)
  • Weight loss
  • Loss of strength
  • Malaise
• 1/3 have perianal involvement (fistulas, fissures, abscesses, skin tags)
  • More aggressive disease if developing fistulas here
  • Be concerned for Crohn's with large, thick skin tags ('elephant ear skin tags'), fissures off the midline, or complex fistulae
  • Can initially present due to perianal disease as index finding
• Complications (see section below)
  • Perforation/abscess
  • Obstruction
  • Bleeding
  • Toxic megacolon
  • Cancer

Extra-intestinal manifestations of IBD common (up to half)

• • Higher prevalence in CD than UC
  • Same complications for UC and CD

Dermatologic	Erythema nodosum (10%) Red painful swollen nodules Usually respond to systemic steroids	Likely to improve after resection of intestinal disease
	Pyoderma gangrenosum (1-12%) Extremely painful ulcerating lesions that typically occur at sites of repeated trauma/surgery/stomas. Key process is neutrophilic dermatosis. Associated with IBD, RA, leukaemia. Avoid debridement. Intralesional steroid injections (triamcinalone), topical steroids or tacrolimus 0.1%, or systemic biologic therapy	Likely to improve after resection of intestinal disease
	Aphthous stomatitis	Useful to differentiate between Crohn's and UC
Rheumatologic	Peripheral arthritis (5-20%) Commonly involving knees or MCPJ
	Spondylitis (1-26%) Particularly men with IBD Inflammatory back pain, especially in lower back or buttocks, in the morning or after rest, which is often relieved by exercise.	Unlikely to improve after resection of intestinal disease
	Symmetric sacro-ileitis (<10%)
	Amyloidosis
Ocular (0.3-5%)	Conjunctivitis
	Uveitis Topical or systemic glucocorticoids
	Iritis episcleritis
HPB	PSC (2-5%)	Unlikely to improve after resection of intestinal disease Higher risk of developing pouchitis
	Autoimmune hepatitis
	Hepatic steatosis
	Cholelithiasis
	Pancreatitis
Renal	Nephrolithiasis (6-23%)
	Obstructive uropathy
	Nephrotic syndrome
Cardiovascular	Hypercoagulable state	DVT, PE, CVA
	Endocarditis
	Myocarditis
	Pleuropericarditis
Bone	Osteoporosis
	Osteomalacia

Workup

• No single diagnostic test for CD - multimodal approach
• Bloods
  • FBE - check for anaemia and thrombocytopaenia
  • UEC
  • LFT (PSC screen)
  • Iron and other nutritional deficiencies
  • CRP < 5 has a >99% sensitivity for active IBD.
  • Serologic markers
    • Antibodies against Saccharomyces cerevisiae (ASCA) - positive in 35-50% of Crohn's, and <1% of UC
    • Perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA)
      • (Helpful in differentiating Crohn's and UC - ASCA positive, p-ANCA negative suggests CD, whereas p-ANCA is more likely to be elevated in UC)
    • Coeliac antibodies
    • QuantiFERON gold if considering immunologics
• Stool studies
  • MCS (rule out infectious causes)
  • Faecal calprotectin
    • Non-specific, but helpful screening tool
    • In general, more elevated in large bowel than small bowel, but often up in both
    • Patients can have quite variable degrees of elevation with their disease, so it's more useful as a marker over time for each patient than as an absolute comparator between patients
    • FC <50mcg/g - sensitivity approaching 100% for colitis
    • FC <50-100 mcg/g = likely quiescent disease
    • FC > 250mcg/g = likely inflammation
  • Faecal lactoferrin
    • >6ng/mL predicts small bowel inflammation at a similar accuracy to calprotectin
• Endoscopy
  • Gold standard for diagnosis
  • Aim for at least two biopsies from five sites, with TI intubation
  • Strictures should be biopsied (24% risk of malignancy in UC and 6% in CD)
  • Expect patchy segmental inflammation
    • Longitudinal ulcers
    • In early CD, plenty of normal mucosa - cobblestone appearance
    • In later CD, hard to differentiate UC from CD due to extensive disease

• Double-balloon enteroscopy allows increased enteral intubation than push enteroscopy or ileocolonoscopy
• Use CD index of severity or Simple Endoscopic Score (below) to quantify disease

• Score decrease of 50% in SES-CD at week 26 correlates with steroid-free remission at week 50

• Capsule endoscopy
  • Only indicated if imaging has shown small-bowel disease, but it is inaccessible to traditional endoscopy
  • Careful use - capsule retention (for longer than 2 weeks) is much higher in CD patients than general population (13% vs 2%)
  • 3 or more ulcers in the absence of NSAID use is considered abnormal
  • Severity measured using the Capsule Endoscopy Crohn Disease Activity Index
• Imaging:
  • MRE (sens 86% spec 93%) / CTE (sens 87% spec 91%) for small bowel inflammation in CD
    • MRE is better than CT in detecting intestinal strictures and ileal wall enhancement, and fistulas and sinus tracts
    • Need to drink 1.5-2L of fluid in the hour prior
  • MRI better for perianal disease
  • CT enterography
    • Mucosal irregularity and hyperdensity
    • Stenosis
    • Prestenotic dilation
    • Mesenteric hypervascularity (comb sign)
  • CT abdo/pelvis
    • Most useful to identify acute complications
  • USS
    • Somewhat useful for detecting TI disease, but very inaccurate for disease proximal to TI
• Operative findings
  • Abdominal
    • Thickened grey-pink or dull purple-red loops of bowel, with areas of thick grey-white exudate or fibrosis of the serosa
    • Involved segments often adherent to adjacent loops or other viscera, possibly with internal fistulas
    • Thickened mesentery with enlarged lymph nodes
    • Skip areas of healthy bowel
      • Uninvolved bowel may be dilated secondary to distal obstruction
    • Fat wrapping (also known as creeping fat) - circumferential growth of the mesenteric fat around the bowel wall
    • Bowel becomes thickened, firm, rubbery and difficult to compress as the disease progresses
  • Bowel mucosa
    • Earliest lesions are superficial aphthous ulcers in the mucosa
    • Ulceration becomes more pronounced over time - characteristically linear
    • Cobblestone appearance - transverse sinuses with islands of normal mucosa in between

Classification

• Inflammation either
  • Penetrating fistulous pattern (20-40%)
    • Most commonly enteroenteric, then enterovaginal
  • Fibrostenotic obstructing pattern
    • Abdo pain, nausea, vomiting
    • Most commonly small bowel involvement
  • Non-stricturing, non-penetrating
  • Classify disease as acute/severe, acute fulminant, active/chronic, chronic, or dormant
• Montreal Classification 2005 to describe location
  • Different to UC Montreal system
  • Again, often used for research
• Crohn disease activity index
  • Mostly used in research
  • Clinical remission achieved when CDAI is below 150
  • Clinical response to therapy with drop of 100 points
  • 150-220 = mild/moderate disease
  • 220-450 = moderate/severe
  • >450 = severe fulminant disease, with likely failed medical therapy and complications

DDx

• IBS
• Small bowel inflammation
  • Lymphoma
  • Eosinophilic gastroenteritis
  • Actinomycoses
  • Behcet's disease
  • Radiation enteritis
• Infection
  • Ileitis
    • Tuberculosis of small bowel
    • Salmonella
    • Shigella
    • Protozoan infections (e.g. amoebiasis)
    • Campylobacter
    • Yersinia
  • Immunocompromised patients
    • Mycobacterial
    • CMV
• IBD undetermined/indeterminate colitis
  • Overlapping characteristics of CD and UC on endoscopic biopsy
  • 10-15% of patients with IBD fall in this category
  • More likely in fulminant disease where the degree of inflammation interferes with precise diagnosis

UC

Characteristic	Ulcerative colitis	Crohn disease
Disease distribution	Colon and rectum	Commonly affects terminal ileum May involve any part of the gastrointestinal tract (ie, mouth to rectum)
Skip lesions (ie, spatially intermittent bowel inflammation)	Rare	Common
Vascularity of the mucosa	Friable mucosa with loss of vascularity	Normal vasculature adjacent to inflamed mucosa
Ulceration	Mainly mucosal Transmural only in severe colitis	Aphthous ulcers: Small discrete mucosal ulcers Transmural ulcers: Deeper ulcers that involve the colon wall
Cobblestone appearance	Not seen	Common
Stricture	Rare	Common
Fistula	Rare	Common Examples include perianal, enterocutanous, or rectovaginal fistula
Perianal disease	Rare	Common Examples include perianal fistula or deep anal fissure

Management goals

1. Incurable disease - aim for induction and maintenance of clinical remission
2. Avoidance of treatment-related toxicity
3. Avoidance of corticosteroids
4. Improved quality of life
5. Prevention of disease complications, including cancer

Principles

• Induce remission with a top-down approach
  • Start on oral steroids then attempt to wean
  • If unable to wean, treat as moderate-severe disease
• Maintain remission with step-up approach
  • More traditional
  • Aminosalicylates -> steroids -> immunomodulators -> biologics
• Treat-to-target
  • Target endoscopic healing - poor association of inflammation with symptoms. Leads to less surgery and less admissions.
  • CDAI can guide symptomatic response (under 'classification')
• Tight control
  • Therapeutic drug monitoring - use trough levels combined with symptoms to decide whether disease management is optimal
  • Use symptoms and biomarkers (CRP and FC) to predict recurrence and step up therapy
• Minimise treatment toxicity
• Monitor for complications

Lifestyle

• Dietary
  • Low-fibre diet can help diarrhoea and pain during an acute exacerbation
  • Frequently need vitamin supplementation - especially vitamin D, B12, folic acid, iron, zinc, calcium, magnesium
  • Exclusive Enteral Nutrition (EEN) is used as an alternative to pharmacological induction agents. This consists of exclusive intake of elemental or non-elemental resource drinks during an acute flare. This is first-line induction therapy in children and second-line in adults (when steroids or biologics are contraindicated), for mild flares. The mechanism is not fully known but may be reduced exposure to antigens in food, altered microbiota, and improved nutritional deficiencies.
  • Has been research into elemental diets to maintain remission, but not thought to be particularly important
• Smoking
  • Clearly affects disease course - increases incidence of relapse and failure of maintenance therapy, and is associated with severity of disease

Drug options:

• Aminosalicylates (a.k.a. 5-aminosalicylate or 5-ASA)
  • More useful in UC than Crohn's
  • Exact mechanism of action unknown, but speculated to decrease prostaglandin and leukotriene synthesis
  • Folic acid supplementation required
  • More useful in UC than Crohn's
  • Can be given orally or rectally
  • Formulations:
    • Mesalazine/mesalamine are drugs in the 5-ASA class, along with olsalazine and balsalazide
    • Azulfidine/Salazopyrin - sulfasalazine (mesalazine with sulfapyridine molecule (an obsolete antibiotic) still attached - brand name Azulfidine). Clear benefit for colonic CD, but controversial for purely small bowel disease since 90% of it is released in colon. Can't have this with sulfa allergies.
    • Pentasa - slow release of mesalazine though the small bowel and colon, starting in duodenum.
      • Interstitial nephritis (1%) - need regular UEC
      • Can be for UC or Crohn's
    • Asacol (contains mesalazine) - only begins to be released in TI, then coats entire colon
    • Salofalk/Mesasal/Claversal (mesalazine) - released starting in ileocaecal region. Used for UC.
    • Mesavant - mesalazine released throughout colon and rectum
    • Dipentum (olsalazine) - colon
    • Colazide/Colazal (balsalazide) - colon
• Corticosteroids
  • Inhibit the production of pro-inflammatory mediators
  • Fast-acting and effective at inducing remission, but not ideal as maintenance therapy (no more effective than placebo, do not induce mucosal healing, and have long-term adverse effects)
  • Budesonide - useful due to high first-pass metabolism, allowing targeted GIT therapy. Used at 9mg/day (controlled release) when active mild-mod disease is confined to ileum or right colon.
  • Prednisolone - good for mod-severe disease at 40-60mg daily until resolution of symptoms and resumption of weight gain.
  • Parenteral steroids (hydrocortisone) are used in severe disease, as long as there is no abscess, and should be tapered once there is clinical improvement (by 5-10mg per week until 20mg, then 2.5-5mg/week until cessation)
• Antibiotics
  • No more effective than placebo in inducing remission
  • Clear role for septic complications
  • Beneficial in perianal disease
• Immunomodulators/suppressors
  • 'Steroid-sparing' medications - normally used once patients have been unsuccessful in weaning off steroids once or twice
    • Effective in maintenance therapy and for the treatment of mod/severe CD
    • Slow onset (3-4 months) - steroids are needed in induction until the transition to immunomodulators is complete
    • Side effects of pancreatitis, hepatitis, fever and rash, but considered relatively safe
  • Thiopurines: AZT (azathioprine (Imuran))/6-MP (mercaptopurine) - both effective in maintaining steroid-induced remission. Purine analogues which inhibit cell proliferation, and suppress cell-mediated events by inhibiting the activity of cytotoxic T cells and NK cells.
    • TPMT (thiopurine methyltransferase) is the enzyme responsible for metabolising AZT and 6-MP and has significant polymorphisms - need to use it to regulate therapy, as low levels can predict adverse effects such as bone marrow suppression, leucopoenia, pancreatitis, hepatitis, fevers and rashes. Need to test for it before starting therapy.
  • MTX (methotrexate) - folic acid antagonist - both induction and maintenance therapy. Can be given IM. Inhibits T cell activation and suppression of intracellular adhesion molecule expression by T cells. Down-regulates B cells. Inhibits methyltransferase, which leads to de-activation of enzyme activity that is important to immune cell function. Leads to hepatotoxicity, ulcerative stomatitis, BM suppression, pneumonitis, pulmonary fibrosis and kidney failure. Teratogenic.
• Biologic agents
  • Monoclonal antibodies, which target mediators of the inflammatory response.
  • Similar safety profiles
    • Increased risk of TB activation/invasive fungal and other opportunistic infections
    • Demyelinating CNS lesions
    • Activation of latent MS
    • Exacerbation CCF
    • Increased risk of melanoma
  • Treatment failure on anti-TNF agents
    • Measure serum drug concentrations and anti-drug antibodies
    • If low concentration, increase dose
    • If anti-drug antibodies, switch agent
    • If both ok, switch to another drug class
  • Infliximab (Remicade/Inflectra/Renflexis) - chimeric monoclonal antibody to TNF-⍺.
    • Efficacious and safe as induction and maintenance monotherapy for mod/severe CD.
    • Highly effective in penetrating and extra-intestinal disease.
    • Results in perineal fistula closure in 65% of patients.
    • Not every patient responds
    • Levels can be measured - aim for >5microg/mL
  • Adalimumab (Humira/Amjevita/Cyletzo/Hadlima) - humanised IgG1 monoclonal antibody to TNF-⍺.
    • Maintenance agent that can be self-administered
    • Levels can be measured - aim for >5microg/mL
  • Certolizumab (Cimzia) - humanised antibody fragment to TNF-⍺.
    • Ideal in pregnant and breastfeeding women as it does not cross placenta or get excreted in breast milk
  • Novel therapies
    • Natalizumab (Tysabri) - recombinant humanised monoclonal antibody against ⍺4 integrin
      • Refractory CD
    • Vedolizumab (Entyvio)
      • Anti-integrin therapy - prevents lymphocyte migration into intestinal tissue
      • Induction of remission, but very slow onset of action
      • Used in those with a poor response to anti-TNF or immunosuppressants
    • Ustekinumab (Stelara) - humanised IgG1 monoclonal antibody targeting IL-12/23
      • Effective in severe CD which is refractory to anti-TNF therapies
      • Also good for psoriasis
    • Upadacitinib (Rinvoq)
      • JAK-1 inhibitor (second-gen JAK inhibitor, more selective than previous)
      • Only approved by FDA since 2022 for IBD, for patients who do not respond adequately to anti-TNF agents
      • Response speed varies from days to 12 weeks
      • Can be used for both induction and maintenance

Medical management (based on eTG 2/1/23)

• Induction
  • Mild-mod: Prednisolone/prednisone 40-50mg daily in the morning until clinical response, taper over 6-8 weeks. For ileocaecal disease, consider an enteric-coated preparation of budesonide (Entocort or Budenofalk), particularly for patients with a history of adverse reactions to systemic steroids, or precautions to their use (diabetes) - 9mg PO daily in the morning for 4-8 weeks, then taper over 2-4 weeks in 3mg increments to stop.
    • Antibiotics only if there is a confirmed infection
    • After 3 months, if no response, consider TNF inhibitor eg infliximab
  • Severe: hydrocort 100mg q6h IV or methylprednisolone 60mg IV total daily, in single or divided dose
    • Generally give IV for 3-7 days depending on response. Switch to PO corticosteroids when disease activity has subsided.
    • Antibiotics only if confirmed infection
    • Alternatives/refractory disease: biologics - infliximab/updacitinib
• Maintenance
  • Most patients need ongoing maintenance therapy
  • Biologics can maintain remission if they were successfully used for induction
  • Thiopurine therapy: azathioprine 2-2.5mg/kg PO daily OR mercaptopurine 1-1.5mg/kg PO daily
  • Methotraxate 10-25mg subcut or IM, once per week OR 10-25mg PO weekly PLUS folic acid 5-10mg PO weekly on a different day
  • Luminal or fistulising CD that is refractory to above therapy should be given a biologic
• Perianal Crohns disease:
  • Metronidazole 400mg BD OR ciprofloxacin 500mg BD is appropriate for active perianal CD. Therapy may be needed for weeks to months.
  • Complex perianal disease should have a TNF inhibitor
• Ileal malabsorption (bile salt diarrhoea)
  • Cholestyramine 2-4g PO daily, with all other drugs taken at least 1 hour prior or 4-6 hours afterwards
  • Need B12, iron and fat-soluble vitamin supplementation

Surgery

• 70% of patients will require bowel resection within 15 years of diagnosis
  • Pre-op
    • Medical optimisation - correct anaemia, treat malnutrition (TPN), literature says can operate on infliximab
  • Post-op
    • Clinical monitoring
    • Endoscopic surveillance 6-12 months for recurrence
• Minimise surgery, and extent of surgery
  • Operative treatment of a complication should treat only that complication - don't attempt to resect more bowel, even if disease is grossly apparent
• General indications:
  • Neoplastic and pre-neoplastic lesions
    • Total proctocolectomy is preferable to segmental resection if this occurs in colon
  • Obstructing stenoses
  • Suppurative complications
    • Fistula (rarely requires operation unless the fistula involves bladder, vagina or skin)
    • Abscess not amenable to conservative management
  • Medically intractable disease, including growth retardation
  • Haemorrhage
  • Free perforation
  • Steroid dependence
• General tips for operating
  • Suture ligate mesenteric pedicles rather than simply tying - risk of haematoma/bleeding due to thick, stiff and vascular mesentery
  • Low threshold for giving a stoma, if patient is nutritionally depleted. Mostly do a double-barrelled stoma.
• Common situations/general advice
  • Operating for RIF pain - acute ileitis found with normal appendix
    • Resect appendix if caecum and appendix appear normal - remove potential cause of pain in the future
    • Do not resect ileum
  • Known CD and concomitant appendicitis
    • If base is healthy, resect as normal
    • If base/caecum are unhealthy, consider either treating with antibiotics or performing an ileocaecectomy
  • Stricturing disease causing obstruction
    • See below under 'obstruction'
  • Initial resection of short segment of diseased TI
    • Also resect caecum unless there are >6 inches of uninvolved TI distal to diseased segment, as there is highly likely to be a recurrence in this segment
  • Bypass procedure
    • Indications:
      • Severe gastroduodenal disease not amenable to stricturoplasty
      • Older poor-risk patients
      • Patients who have had several prior resections and cannot afford to lose any more bowel
      • Resection would necessitate entering an abscess or endangering a normal structure
  • Penetrating disease
    • Enteroenteral fistula - not itself an indication for surgery in the absence of sepsis. Medical management with anti-TNF drugs is best.
    • Enterocutaneous fistula - rarely spontaneous, most likely after bowel resection or drainage of an intra-abdominal abscess. May close spontaneously. Follow usual ECF protocol. If conservative management fails, excise the fistula tract and perform a primary anastomosis.
    • Fistula between bowel and other viscera - excise the diseased segment of bowel and the fistula tract, and close the defect in the viscera primarily.
    • Ileosigmoid fistula - only excise the sigmoid if it is also diseased, which is rarely the case.
  • Perianal disease
    • Aim for non-operative treatment unless an abscess or complex fistula develops - trial one month metronidazole (or ciprofloxacin), another month antibiotics, then consider seton
    • Don't excise haemorrhoids or large anal skin tags
      • Differentiate between oedematous skin tags vs loose/soft skin tags - the latter can reflect less active disease and may be more ok to excise
    • Non-suppurative, chronic fistulisation or perianal fissuring is treated with antibiotics, immunosuppressive agents and infliximab (results in much improved rates of fistula closure)
      • Can often start medical management with infliximab (targeted to degree of persistent luminal disease/other disease activity/drug levels), then consider removing seton once treatment is established - work closely with gastroenterologists
      • If disease control is unable to be established, keep going with setons
      • If disease is well-controlled, consider definitive fistula treatment
    • Operate carefully, with as small of an intervention as possible
    • Liberal placement of drainage catheters and non-cutting setons
    • Superficial, low trans-sphincteric and low inter-sphincteric fistulas - fistulotomy
    • High trans-sphincteric, supra-sphincteric and extra-sphincteric fistulas - non-cutting setons
    • Fissures are usually lateral, relatively painless, large and indolent and often respond to conservative management
    • Drain abscesses without large excisions of tissue
      • Two weeks post-op metronidazole
    • Proctectomy is sometimes required for patients who have persistent and unremitting symptoms despite conservative medical and surgical therapy
  • Duodenal disease
    • Occurs in <5%, most commonly in the duodenal bulb
    • Primary indication for surgery is duodenal obstruction not responding to medical therapy
      • Endoscopic balloon dilation
      • Gastrojejunostomy to bypass
      • Consider stricturoplasty if possible

Endoscopic surveillance

• CD: those with extensive or left-sided colitis should be screened at diagnosis and then every 1-2 years until they have 2 consecutive negative exams, at which point stretch out to 3-yearly. After 20 years of disease, should screen 1-2 yearly again.

Prognosis

• GIT cancer is the leading cause of disease-related death

Complications

Localised peritonitis

• Presentation with local guarding, RIF pain and fevers suggests contained micro-perforation
• Once CT has excluded abscess, medical management should be undertaken with one month of antibiotics (initially IV)
• The role of steroids is controversial - those already on them can continue, but those not on them would probably have a higher rate of complication with steroids
• Non-responders or recurrent episodes warrant resection

Perforation and abscess

• Perforations can occur anywhere in GIT - secondary to either penetrating ulcer or upstream from a stricture
  • Caecal perforation occurs in setting of LBO secondary to colonic stricture - needs subtotal colectomy with end ileostomy
  • Focal perf secondary to segmental disease - needs either segmental resection and primary anastomosis or Hartmann's. Can be associated with a fibrosing stricture, which may need resection.
• Free perforation and generalised peritonitis
  • Uncommon (more common to have a fistula to another viscera, or contained abscess)
  • Resect the segment of involved bowel, with a primary anastomosis if there is minimal contamination, and an ostomy if generalised peritonitis is present or the patient has compromised immune system or nutrition (reverse in 4-6 weeks)
• Abscesses are especially common in caecum/ileum secondary to micro-perforation - can be intraperitoneal, extraperitoneal, or intra-mesenteric
  • Initial management
    • Antibiotics - ciprofloxacin and metronidazole first-line
    • Percutaneous drainage if possible (step up to surgical drainage if not)
      • Well-defined abscesses <3cm may be treated medically
    • Stop/reduce steroids and immunomodulators (involve gastro)
    • Optimise nutrition for planned resection - TPN vs EEN
    • Wait 3-5 days for improvement
      • >90% of cases improve with drainage, others require elective bowel resection (better outcome if you can get them through to elective procedure in a clean field)
  • Subsequent management:
    • Either semi-elective resection of the involved segment in 5-7 days (classical approach) or medical treatment with immunomodulators

Obstruction

• Much more common in CD than UC - intermittently - can be inflammatory/fibrotic stricture, but can also be adhesive due to previous surgery
• Aetiology
  • Secondary to an acute exacerbation of active disease
    • Typically improve with medical management (IV corticosteroids)
  • Secondary to chronic fibrosing lesions (most patients with complete SBO fall into this group)
    • Most commonly TI
    • Trial non-op - often partial obstruction
      • No benefit to steroids - often require surgery - complete obstruction often requires resection
      • If doubt over presence of acute inflammation, can do faecal calprotectin
    • Look to intervene if no improvement in 48 hours, according to Schein
      • Operation of choice is segmental resection and primary anastomosis
      • Consider stricturoplasty - when bowel resection is inappropriate due to risk of short bowel syndrome in patients with extensive fibro-stenotic disease, or in patients with multiple short-segment strictures over a longer area of bowel, several previous bowel resections, and in those with chronic fibrous obstruction. Complication and recurrence rates are comparable to resection with anastomosis in this setting.
      • Endoscopic dilation - initial success rate 90% for fibrotic strictures however 75% of patients require further dilation
      • Needle-knife stricturotomy can also be used - not widely-accepted yet
      • Large bowel strictures, particularly UC, raise concern for malignancy. Do a full oncologic resection if operating in this setting. Stricturoplasties are not recommended in colon.

Bleeding

• Large-volume bleeding is rare to be truly caused by IBD - consider alternatives such as PUD
• Can get erosion into a vessel from a CD ulcer, particularly duodenal CD
• If small bowel, may need resection with primary anastomosis
• Duodenal bleeding can usually be treated endoscopically, with duodenotomy and oversewing of the bleeding area as a backup
• Initial management
  • Resus
  • ?saline-adrenaline enemas
  • NGT with gastric lavage (?UGIB) -> gastroscopy +/- colonoscopy
  • Consider CT angio
  • Surgery if continued haemorrhage despite 6+ units pRBC, or other indications

Toxic megacolon

• Occurs in Crohn colitis and UC
• Marked colonic dilation, abdominal tenderness, fever and leucocytosis
• See separate topic

Bowel cancer

• Carcinomas typically arise at sites of chronic inflammation, especially TI
• Epidemiology
  • OR 100 for small bowel cancer compared to normal population, but absolute risk still low
  • 2.2% risk at 25 years since diagnosis
• Pathophysiology
  • Follows standard dysplasia sequence
  • Risk related to extent of small bowel involvement and duration of disease
  • Small bowel adenocarcinoma associated with CD behaves aggressively - strong probability of extracellular mucin
  • Mucinous-appearing anal fistulas and ileal areas of adhesion/retraction should always be closely examined by a pathologist to evaluate for dysplasia or malignancy
• Presentation
  • Suspect in patients who develop a change in their clinical status, such as an obstruction that fails to resolve with usual treatments
  • Diagnosis rarely made pre-operatively
• Poor prognosis due to frequent late detection

Ureteral obstruction

• Occurs secondary to ileocolic disease with retroperitoneal inflammatory compression
• Aim to treat the primary ileocolic disease surgically, which is usually adequate
• Less likely to work with longstanding disease - may require ureterolysis +/- stenting

Crohn's disease in pregnancy

• Disease activity influences rate of pregnancy and fetal complications
• Try to avoid procedures, including endoscopy, if possible
• Limit metronidazole to short courses, and avoid ciprofloxacin. Augmentin DF is safer.
• 5-ASA is safe. Steroids are low-risk. Thiopurines should be continued if they are monotherapy. MTX is contraindicated. Anti-TNF agents should be continued, but certolizumab is favoured because it does not cross the placenta. Upadacitinib should be avoided.
• Surgery is ideally performed in the second trimester.
• Those with active perineal disease or rectal involvement should have a LUCS.
• Vaginal delivery is ok with a stoma.