Crohn's disease

• Background

  A type of inflammatory bowel disease.

  Pathophysiology

  • Skip lesions anywhere from mouth to anus, though terminal ileum is most commonly affected.
  • Transmural granulomatous inflammation.

  Epidemiology

  • Prevalence: 1/600.
  • Bimodal onset: 15-30 years (commoner) and 60-80 years. Commoner in kids than UC.

• Signs and symptoms

  Symptoms:

  • Diarrhoea: bloody in around 25%. May also have steatorrhea.
  • Lower abdominal pain, especially RLQ.
  • Weight loss.
  • Fever
  • Fatigue

  Relative to UC, it is more likely to present acutely.

  Signs:

  • Perianal: abscesses, fistula, tags.
  • Right iliac fossa mass from inflammation of terminal ileum.

  Non-intestinal:

  • Aphthous ulcers.
  • Eyes: uveitis, episcleritis, conjunctivitis.
  • Clubbing
  • Erythema nodosum, pyoderma gangrenosum.
  • MSK: entero-arthritis (usually large joints such as knee), sacroiliitis.

  Hepatobiliary:

  • Gallstones
  • Chronic hepatitis, NAFLD, and cirrhosis.

• Risk factors

  • Smoking
  • Family history.
  • NOD2 mutation.
  • White ethnicity.

• Investigations

  Bloods:

  • ↑CRP/ESR in active disease. Other signs of inflammation: ↑platelets, ↓albumin.
  • Hb and haematinics (iron studies, B12, folate): ⅓ patients have anaemia, usually anaemia of chronic disease or iron deficiency. Less commonly, ↓B12 or ↓folate anaemia.
  • U+E, Mg2+, and Ca2+ for nutritional deficiencies.
  • LFT for associated hepatobiliary disease.
  • Immunological: anti-Saccharomyces cerevisiae antibodies (70% in Crohn's), pANCA (70% in UC). Not routinely checked.

  Stool:

  • Culture to rule out infection.
  • Faecal calprotectin as a marker of inflammation, 93% sensitive and 96% specific for IBD.
  • C. diff toxin. Presence is a poor prognostic marker.

  Ileocolonscopy with biopsy:

  • Endoscopy shows skip lesions, cobblestone appearance, aphthous ulcers.
  • Biopsy shows transmural disease with granulomas. Crypt changes may be seen, but are commoner in UC.

  Imaging:

  • Abdominal XR: dilation, sacroiliitis, abscess.
  • CT/MRI abdo for info on disease extent. May show skip lesions, abscess, and fistulae. Barium enema is an alternative, showing small bowel strictures.

• Management

  Medical

  Inducing remission in attack:

  • Methylprednisolone IV 3 days then prednisolone PO 2 weeks.
  • Consider budesonide PO in isolated ileo-cecal disease.
  • If refractory: add azathioprine or mercaptopurine, or add/switch to a biologic.
  • Enteral nutrition therapy (aka exclusive enteral nutrition) for 6-8 weeks is a non-drug alternative, using either a polymeric formula (drinkable) or elemental formula (via NG tube, since it's too gross to drink). In adults it is less effective than steroids, but in kids it may be more effective and less likely to affect growth.

  Maintaining remission:

  • If mild, may not need treatment beyond smoking cessation.
  • Indications for treatment: frequent relapses, ≥2 steroid courses per year, or relapse <6 weeks after stopping steroids.
  • Azathioprine or mercaptopurine are 1st line.
  • Further options: methotrexate (avoid in women of childbearing age), biologics.

  Biologics:

  • Can be used for induction and maintenance in refractory severe disease.
  • Anti-TNFα: infliximab, adalimumab.
  • Other agents: vedolizumab (anti α4β7-integrin), ustekinumab (anti IL-12 and IL-23).

  Other considerations:

  • Symptomatic relief: loperamide and an antispasmodic, but not during attacks.
  • Upper GI disease: PPI.
  • Perianal disease: metronidazole PO and/or ciprofloxacin PO, topical mesalazine. Fistulae may need seton insertion, a silicone string in the tract which allows drainage and healing.
  • MDT approach including dietician and stoma nurse.

  Surgical

  Needed in 70%.

  Indications:

  • Medically refractory.
  • Obstruction or perforation.
  • Growth failure.

  Small bowel procedures:

  • Resection and anastomosis.
  • If extensive, may cause short gut syndrome, characterised by diarrhoea, steatorrhea, electrolyte abnormalities, malnutrition including vitamin deficiencies, weight loss, and fatigue.
  • Strictureplasty is a bowel-sparing technique used to minimize resection and short gut syndrome.

  Large bowel procedures:

  • If the rectum is affected, panproctocolectomy with ileostomy.
  • Otherwise, subtotal colectomy with ileorectal anastomosis.

  Post-op recurrence:

  • 30% recurrence in 1 year, with 10% more each following year. Risk increased if smoking.
  • Consider azathioprine plus 3 months metronidazole to maintain remission post-op.

  Long term surgical complications:

  • Vitamin B12 deficiency, especially if >20 cm removed. Replace B12 parenterally.
  • Bile salt malabsorption. Diagnose with SeHCAT scan, treat with cholestyramine.

• Complications

  • Small bowel obstruction: bowel thickening and fibrosis leads to stricture.
  • Abcess
  • Fistula
  • Colorectal carcinoma, though less than in UC.
  • Disease relapse is common, even after surgery.

• Azathioprine

  Mechanism

  • A pro-drug for mercaptopurine.
  • Inhibits purine and hence DNA synthesis, affecting fast-proliferating cells like lymphocytes.

  Management

  • Check TPMT activity first. If low, contraindicated due to pancytopenia risk.
  • Monitor FBC for pancytopenia and LFT for hepatitis. FBC may also show macrocytosis.

• Stomas

  Definition

  • A stoma is a connection between a viscus – usually bowel – and the skin.
  • It typically follows surgery for inflammatory bowel disease (IBD), colorectal carcinoma (CRC), or diverticular disease.

  End vs. loop stomas

  End stomas:

  • Usually permanent and have a single lumen. Exception is temporary end colostomy in Hartmann's.
  • Used after bowel resection when there is insufficient distal bowel to anastomose with.
  • Also used for palliating unresectable cancer, or, in extreme cases, for constipation or faecal incontinence.

  Loop stomas (aka defunctioning stomas):

  • Usually temporary, 'defunctioning' a distal segment of bowel – i.e. preventing the flow of GI content to it – to allow anastomosis healing or if there is an anastomotic leak. Also used to defunction a fistula, and in emergency treatment of obstruction.
  • Formed by partially cutting a loop of bowel, creating an afferent (proximal) limb which replaces the anus, and an efferent (distal) limb which just secretes mucus (a 'mucus fistula').

  Ileostomies

  • Right lower quadrant stomas are usually ileostomies.
  • Everted and formed into spout, which is several centimetres clear of skin to reduce the irritant effect of small bowel effluent.
  • Effluent is usually continuous and liquid.
  • End ileostomies typically follow pan-proctocolectomy or subtotal colectomy (IBD, especially UC).
  • Loop ileostomies allow healing of a distal anastomosis after anterior resection or left hemicolectomy (CRC).

  Colostomies

  Overview:

  • Flush with skin as large bowel content is less irritant.
  • Commonly used in colon cancer and diverticular disease.
  • Produces intermittent, solid effluent.

  Right upper quadrant stomas:

  • Usually loop (defunctioning) transverse colostomy, to alleviate or prevent obstruction from inoperable distal cancer.

  Left lower quadrant stomas:

  • End colostomy: temporary after Hartmann's, or permanent after abdominoperineal resection of anus and rectum.
  • Loop colostomy: sigmoid bought to surface, to alleviate or prevent obstruction from inoperable distal cancer.

  Urostomies

  • An 'ileal conduit' is formed in which the ureters are diverted into a resected portion of ileum, which then forms a stoma with the abdominal wall.
  • Look like ileostomies, but distinguished by the content of the bag.

  Stoma bags

  • Can be single piece bags – attaching directly to skin – or two piece bags, in which one part sticks to the skin and the bag is attached to that.
  • Can have a second hole to allow regular drainage, or be closed for those who don't need frequent changes.

  Complications

  Short term:

  • Bleeding, infection.
  • Leaking and skin irritation.
  • Necrosis due to vascular compromise.
  • High output (>1.5 L/24h), especially ileostomy. Management: maintain hydration, check electrolytes, monitor losses, give IV fluid.
  • No output. Consider obstruction and manage accordingly: NBM, bloods, CXR and AXR, IV fluids, NG tube.

  Long-term:

  • Prolapse of bowel through stomal opening.
  • Parastomal hernia.
  • Stenosis
  • Psychosexual problems.