Crohn’s disease and Ulcerative colitis

	Crohn’s Disease	Ulcerative Colitis
Epidemiology	Younger people Smokers – 3-4 times more common Racial preference: Jewish & Caucasian	Younger people Non-smokers – smoking seems protective for UC (many patients with UC may present after smoking cessation)
age	Peak onset: 15-30 years Can also present in children – FFT and also in those in their 60’s	First peak onset 15-25 years (up to age 40 years) Second peak onset > 50 years
Risk factors	Tobacco Abuse Oral Contraceptives Antibiotics Frequent NSAIDs Urban environment1 o relative with Inflammatory Bowel Disease Minimal increased Colon Cancer risk (contrast with Ulcerative Colitis)	Specific Bacterial Gastroenteritis infections (Nontyphoid Salmonella, Campylobacter, ,Clostridioides difficile) Family History confers – Monozygotic twin: 95 fold increased risk Higher risk with refined sugar intake and soda intake, increased meat and fat intake
Regions involved	Transmural disease (Granulomas) that may affect any part of the GIT Commonly – Terminal ileum & colon Can affect mouth to anus Skip lesions	Mucosal disease (no Granuloma)confined to the colon Begins at the rectum and Retrograde extension and Continuous Ulcerative Proctitis 🡪 Proctosigmoiditis 🡪 Pancolitis
Clinical presentation	Adult (strongest associations first): Perianal lesions: fistulae Abscesses Strictures Weight loss in 3 months Abdominal pain >3 months Nocturnal diarrhea Fever Abdominal pain subsides for 30-45 minutes after meals No rectal urgency Mass often at the right lower quadrant (common) Obstruction (due to stricture, fistula, or abscess) Child (strongest associations first): Anemia Hematochezia Weight loss Vitamin malabsorption Malnutrition (common) Abdominal distension (common) Extra-intestinal symptoms (common)	Classic: Intermittent bloody diarrhea (most common presenting complaint) Rectal or fecal urgency Tenesmus Abdominal pain (often in the left lower quadrant) Fever Malaise Weight loss Additional features: No vitamin malabsorption (ileum typically not affected) Malnutrition (occasionally) Abdominal distension (if severe) Extra-intestinal symptoms (rare), such as primary sclerosing cholangitis (PSC) and thromboembolic events

Extra-intestinal symptoms	extraintestinal findings are more common with Crohn’s Disease Joints:  – migratory polyarthritis (5-21% of cases) – sacroiliitis – ank spon Skin:  – erythema nodosum – pyoderma gangrenosa – Clubbing – Psoriasis – Aphthous Stomatitis, Aphthous Ulcers or Canker Sores (4%) Eyes:  – Uveitis – episcleritis – iridocyclitis Liver:  – Primary Sclerosing Cholangitis (4-5% co-Incidence) – Hepatic Steatosis  – Cholelithiasis Autoimmune: – celiac – thyroid Bones : – osteopenia/osteoporosis – osteomalacia Blood : – anaemia Rare (bronchitis, bronchiectasis, other lung disease, hyperhomocysteinemia, pancreatitis, renal stones, thromboembolism, PSC, cholelithiasis, nephrolithiasis)
Investigations	Bloods: – CRP: shown to correlate with clinical, endoscopic and histologic disease activity persistent elevation is associated with a higher relapse rate and better response to infliximab anemia of chronic disease (normocytic, normochromic) – ESR – WCC – hypoalbuminemia – pANCA +ve 🡪 UC – ASCA +ve 🡪 CD Other: – IS, Mg, B12 (absorption issues), LFT & INR, Coeliac Ab Stool cultures:  – to r/o infective causes – Faecal Calprotectin Imaging: – AXR: string sign (due to hypertrophy of intestinal wall  narrowing of GIT) – Abdo USS or CT scan (regions of narrowing & dilation) – CT enteroclysis – contrast is infused via a nasogastric tube – MRI – Colonoscopy & biopsy  – never perform in acute presentation/ flare 🡪 +++ pain & risk of perforation Barium enema:  – cobble stone, rose thorn ulcers, colon strictures & proximal dilation – now rarely used in IBD and has been replaced by colonoscopy
Complications	Obstruction Fistula Perforation Peritonitis Perianal disease – fissures, fistulas, skin tags, ulcers Other: Cancer (but less common than in UC), Malabsorption	Cancer +++ (increased with duration of UC, extent of UC, concurrent PSC, persistent mucosal inflammation, dysplasia Toxic mega colon (rare)

Faecal Calprotectin

• Differentiation of Noninflammatory vs. Inflammatory Conditions
  • Noninflammatory Conditions: FC assists in differentiating conditions like irritable bowel syndrome (IBS).
  • Inflammatory Diseases: FC helps identify inflammatory bowel diseases (IBD), guiding further investigations.
• Clinical Decision-Making in IBD Management
  • Utility in Management: FC can guide clinical decisions regarding IBD treatment and monitoring.
• FC Levels and Clinical Correlations
  • Mucosal Healing and Histological Remission
    • Threshold for Remission: FC levels < 100 micrograms/g indicate mucosal healing or histological remission in ulcerative colitis (UC) and luminal Crohn’s Disease (CD).
  • Risk of Relapse
    • Predicting Relapse: FC levels prior to therapeutic de-escalation are inversely related to the risk of relapse. FC levels > 100 micrograms/g are associated with a higher risk of relapse within 1 year.
  • Correlation with Endoscopic Inflammation
    • Differentiating Active Disease from Remission: Elevated FC correlates with endoscopic inflammation in UC and CD. FC levels > 250 micrograms/g can differentiate active disease from remission (sensitivity 80%, specificity 82%).
  • Specific Considerations in Crohn’s Disease
    • Small Bowel Crohn’s Disease: Accuracy in Isolated Small Bowel Disease: The accuracy of FC may be lower in CD affecting only the small bowel. Patients with isolated small bowel CD may have normal FC levels despite active disease.
    • Early Detection of Relapse
    • Rising FC Levels Before Symptom Onset
  • Early Indication of Relapse: FC levels may begin to rise 3 months before symptoms of relapse become apparent.

• Medicare Benefits Schedule (MBS) Listing: As part of the 2021-22 Budget, the Australian Government announced that Faecal Calprotectin (FC) testing would be listed on the MBS from 1 November 2021.
• Diagnostic Use: FC testing can be used to differentiate the diagnosis of Irritable Bowel Syndrome (IBS) from Inflammatory Bowel Disease (IBD).
• New MBS Items: Two new items will be listed on the MBS:
  • Item 66522: For FC testing as requested by a Medical Practitioner.
  • Item 66523: For follow-up FC testing as requested by a Specialist Gastroenterologist.

MBS as of 1 November 2021

• Item 66522: FC testing for patients with gastrointestinal symptoms suggestive of inflammatory or functional bowel disease presenting to a Medical Practitioner.
  • Patient Criteria:
    • Symptoms suggestive of inflammatory or functional bowel disease for more than 6 weeks.
    • Age not exceeding 50 years.
    • Infectious causes excluded.
    • Low likelihood of malignancy.
    • No clinical alarms (e.g., unexplained weight loss, anaemia, melaena, rectal bleeding, diarrhea, family history of colon cancer, IBD, or coeliac disease).
• Item 66523: FC testing for patients referred to a Specialist Gastroenterologist, where the initial FC test (66522) was inconclusive (50-100 µg/g) and the Specialist deems an endoscopic examination initially unwarranted.

Treatment

1. The main goals of treatment for ulcerative colitis are to:
   1. Control symptoms (achieve remission)
   2. Prevent symptoms from coming back (maintain remission)

2. Smoking cessation
   1. Strongly associated with negative disease outcomes in CD.
   2. Cessation should be actively encouraged and awareness of available help and resources given

3. Anti-inflammatories
   1. Aminosalicylates (5-ASA) – Local colonic anti-inflammatory effects
      1. eg. Sulfasalazine, mesalazine
      2. for induction and maintenance of remission in mild to moderate UC
   2. Corticosteroids  – Binds to intracellular receptors and modulates expression of multiple pro-inflammatory genes
      1. to induce remission

4. Immunosuppressants/ immunomodulators
   • Azathiopurine – Decrease DNA replication in highly proliferative cells, including lymphocytes
     • for refractory disease/ frequent relapses
   • Methotrexate
   • TNF α inhibitors  – Immunoglobulins that neutralise soluble and membrane-bound TNF, a pleotropic pro-inflammatory cytokine
     • Infliximab – Remicade
     • Adalimumab – Humira

5. Given the risks of infection, vaccination and screening have become important issues in IBD
   1. screening for
      1. tuberculosis
      2. hepatitis B infection 
      3. VZV
      4. HIV
      5. MMR
      6. Syphilis

before initiating therapy

1. advice regarding travel (eg. avoid travelling to areas where tuberculosis is endemic if taking an anti-TNF agent).
2. Vaccinate all with necessary non-live vaccines

1. Influenza vaccination
2. Pneumococcus
3. Covid
4. Live vaccinations should not be given if receiving thiopurines, biologics or corticosteroids long term
   1. BCG (bacille Calmette–Guérin) vaccine.
   2. Some Japanese encephalitis virus vaccines.
   3. MMR (measles-mumps-rubella) vaccine.
   4. rotavirus vaccine.
   5. oral typhoid vaccine.
   6. varicella vaccine.
   7. yellow fever vaccine.
   8. zoster vaccine (Zostavax)

6. Employment
   1. The ACCESS report revealed over three-quarters of patients noticed a change in work life as a result of IBD. 
   2. This included time off, restriction of duties, travel restriction and loss of income

7. Education
   1. Similar findings to above, as well as a lack of understanding or not being believed about their illness

8. Quality of life
   1. Many studies have shown a lower quality of life in IBD patients and this has been associated with disease activity

9. Diet
   1. eating a well-balanced, nutritious diet
   2. keep a healthy body weight. 
   3. certain foods seem to make symptoms worse. For example, some people feel better if they avoid dairy foods like milk, yogurt, and cheese, while others may find that it helps to adhere to a low-fiber diet

10. Anaemia
    1. Common in IBD and often multifactorial. 
    2. Iron deficiency is common and responds poorly to oral iron.
    3. Intravenous iron is particularly useful in this situation

11. Psychological health
    1. Stress, depression and poor psychological health are associated with chronic disease and increased disease activity.
    2. Many new psychological therapies may help, although evidence on the use of antidepressants is conflicting

12. Sexual dysfunction
    1. The potential for incontinence and wind, and a resistance to discuss sexual health concerns makes these issues common and challenging

13. Functional GI symptoms
    1. Common in IBD and require careful assessment. 
    2. Dietary interventions (via a specialist dietician) have proven useful

14. Nutrition and development
    1. Key priorities in all patients, but should be particularly focused on children, adolescents and young adults
    2. Check iron, vitamin B12 and folate
    3. Replace to normal range. 
    4. 2–5 mg daily of folate is needed in the setting of extensive ileal disease, in those on a fibre-restricted diet and in those taking sulfasalazine

15. Contraception
    1. Preference for long-acting, non–oestrogen containing contraception in patients with active IBD, given the theoretical risk of venous thromboembolism.
    2. Education that there is no increased risk of IBD flare with the use of oral contraceptives.
    3. Reassurance that absorption of oral contraceptives is maintained in those with mild UC or short ileal resections.
    4. Recommendation for non-oral contraceptives in the setting of prior extensive small bowel resection or active small bowel inflammatory disease

16. IBD Activity review
    1. Three months of corticosteroid-free remission
    2. Clinical (assess symptoms)
    3. Biochemical aim for
       1. faecal calprotectin <100–250 μg/g
       2. normalisation of C-reactive protein
    4. Quiescent disease on cross-sectional imaging if available (intestinal ultrasonography, magnetic resonance imaging)
    5. Endoscopic assessment may be warranted if there is discrepancy between clinical symptoms and biochemical or radiological assessment.

17. In pregnancy

Medication	Male fertility	Female fertility	Pregnancy	Commencement for management of flare in pregnancy*	Breastfeeding
Aminosalicylates	Switch to an alternative three months prior to conception attempts	Continue, but use 5 mg daily of folic acid with sulfasalazine	Continue, but use 5 mg daily of folic acid with sulfasalazine	For mild-to-moderate flare of UC. Can commence or dose escalate both topical (enemas or suppositories) and oral formulations.	Continue, but use 5 mg daily of folic acid with sulfasalazine prior to and during pregnancy. Avoid sulfasalazine in breastfeeding.
Thiopurines	Continue	Continue	Continue	Not recommended	Continue
Methotrexate	Continue	Cease at least three months prior to conception	Contraindicated	Contraindicated	Contraindicated
Corticosteroids	Continue	Aim for three months corticosteroid-free remission prior to conception	Avoid prolonged (>6 week) courses or use as a maintenance agent	For moderate-to-severe UC and CD flares, or if inadequate response to aminosalicylates. Commence prednisolone 40 mg daily, weaning by 5 mg weekly, with early gastroenterology assessment. Budesonide controlled release may be trialled.* Avoid prolonged (>6 week) courses and monitor for side effects (glucose intolerance, psychiatric).	Continue at doses <40 mg prednisolone daily
Anti-TNF biologics	Continue	Continue	Continue throughout pregnancy10	For moderate-to-severe flares of UC and CD; can be commenced in pregnancy with specialist supervision.	Continue
Ustekinumab	Continue	Continue	Continue throughout pregnancy10	Minimal safety data for induction available.	Continue
Vedolizumab	Continue	Continue	Continue throughout pregnancy10	Minimal safety data for induction available.	Continue
Tofacitinib	Continue	Cease at least four weeks prior to trying to conceive	Contraindicated	Contraindicated	Contraindicated