1. INFLAMMATORY BOWEL DISEASE
Anusha Reddy
FY1 SWFT
3rd Feb 2014

2. objectives 2 Case Studies: Crohn’s Vs Colitis THINK: AETIOLOGY
EPIDEMIOLOGY
SIGNS AND SYMPTOMS
INVESTIGATIONS
MANAGEMENT

3. Case Study 1 22 Female PC: 6/52 of 5 x loose, non-bloody stools daily
Right lower quadrant abdominal pain (especially after eating)
8kg weight loss
Bilateral knee and ankle pains

4. More information required
Full history
Nil PMH, no hx of foreign travel
No medications or allergies
Current smoker- 5 pack-years
Examination
Definite and moderately tender 5-cm mass in the right lower quadrant
No joint effusion or skin lesions are noted

5. Differential diagnosis
Gastroenteritis
Crohn’s Disease
Ulcerative Colitis
Irritable Bowel Syndrome
Behcet’s Disease
Bowel Cancer
Tuberculosis
Amyloidosis
Acute Appendicitis
Behçet's disease is a complex multi-system disorder of unknown aetiology characteristically presenting with recurrent oral ulcers. It is presumed to be an autoimmune disease and includes involvement of the mucocutaneous, ocular, cardiovascular, renal, gastrointestinal, pulmonary, vascular, musculoskeletal, urological and central nervous systems.  In many patients the activity of this disease diminishes with time.

6. WHAT DO WE THINK THIS IS? 22 Female
PC: 6/52 of 5 x loose, non-bloody stools daily
Right lower quadrant abdominal pain (especially after eating)
8kg weight loss
Bilateral knee and ankle pains

7. Crohn’s Disease- Definition
Chronic Inflammatory Bowel Disease (IBD)
Unknown Aetiology
Characterised by
Focal
Asymmetrical
Transmural
Occasionally granulomatous
inflammation
Any part of the GI tract- mouth anus
It may affect any part of the gastrointestinal tract but particularly the terminal ileum and proximal colon.
Disease is restricted to the small bowel in 30% of patients and the large bowel in 30% of patients. 40% of patients have involvement of the small and large bowel.
Fistulae and strictures may occur.
Unlike ulcerative colitis, there may be unaffected bowel between areas of active disease (skip lesions).
The clinical course is characterised by exacerbations and remission.
Risk factors:
Infectious agents such as Mycobacterium paratuberculosis, Pseudomonas spp. and Listeria spp. have all been implicated. An increase in TNF-alpha, high-fat diets and genetic mutations have all been mooted as possible causes

8. Crohn’s Disease- Epidemiology
Incidence: per 100,0001
Prevalence: 115,000 in the UK
Age of onset: 2 peaks 1) Y (more common)
2) Y
Female: Male 1.8:1 Children this is reversed!
Risk Factors2
Mycobacterium paratuberculosis, Pseudomonas spp. & Listeria spp.
↑TNF-alpha
High-fat diets
Genetic mutations
1) Steed H, Walsh S, Reynolds N; Crohn's disease incidence in NHS Tayside. Scott Med J Aug;55(3):22-5
2) Rangasamy P et al; Crohn Disease, Medscape, Jun 2011

9. Crohn’s Disease- Symptoms
Abdominal pain, cramping or swelling
Anaemia
Fever
Gastrointestinal bleeding
Joint pain
Malabsorption
Persistent or recurrent diarrhoea
Stomach ulcers
Vomiting
Weight loss

10. Crohn’s Disease- On Examination
General ill health- weight loss & dehydrated
Hypotension, tachycardia and pyrexia
Abdominal tenderness or distension, palpable masses.
Anal and perianal lesions (abscesses, fistulae)
Mouth Ulcers
Extra-intestinal manifestations of Crohn’s

11. Crohn’s Disease- Extra Intestinal
Crohn’s disease is associated with extraintestinal manifestations that may be more problematic than the bowel disease. Colitic arthritis is a migratory arthritis that affects knees, ankles, hips, wrists, and elbows that may accompany Crohn’s disease (although it is uncommon when Crohn’s is confined to the small intestine). Often, joint pain, swelling, and stiffness parallel the course of the bowel disease. Successful treatment of the bowel disease results in improvement in the arthritic symptoms. Pericholangitis, usually associated with primary sclerosing cholangitis (PSC), is the most common hepatic complication of inflammatory bowel disease. PSC is demonstrable by endoscopic retrograde cholangiopancreatography (ERCP) or hepatic magnetic resonance imaging (MRI). Pericholangitis is characterized by inflammation of the portal tracts with lymphocyte and eosinophil infiltrates. Degenerative changes in the bile ductules are also characteristic. Kidney stones (calcium oxalate stones) are seen in patients with small-intestine Crohn’s disease. Inflammation from the bowel can result in urinary tract complications. Occlusion of the ureters, leading to obstruction and hydronephrosis, usually involves the right ureter in Crohn’s patients. Fistula can form between inflamed bowel and the urinary bladder leading to infection (Figure 8).

12. Investigations Bloods Stool culture and microscopy
FBC, CRP, U&Es, LFTs
Stool culture and microscopy
anti-S. cerevisiae antibodies Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) (UC>CD)
Abdo Xray
Ileocolonscopy and biopsy from the terminal ileum as well as the affected sites
Small bowel follow through
If upper GI symptoms- Upper GI endoscopy
If lower GI symptoms- Flexible sigmoidoscopy/EUA
-Serum levels of CRP are useful for assessing a patient's risk of relapse. High CRP levels are indicative of active disease or a bacterial complication. CRP levels can be used to guide therapy and follow-up.
-Antibodies to the yeast Saccharomyces cerevisiae (ie anti-S. cerevisiae antibodies (ASCA)) are more common in Crohn's disease than in ulcerative colitis. Perinuclear antineutrophil cytoplasmic antibody (p-ANCA), is more common in ulcerative colitis than in Crohn's disease. These two tests are sometimes useful in differentiating the two conditions but they are not particularly specific and need to be combined with clinical assessment.
-For suspected Crohn's disease, ileocolonoscopy and biopsies from the terminal ileum as well as each affected colonic segment, to look for microscopic evidence of Crohn's disease, are first-line procedures to establish the diagnosis.
Ileocolonoscopy defines the presence and severity of morphological recurrence and predicts the clinical course, so is recommended in all patients where recurrence is suspected.[7]
-In a patient with evidence of Crohn's disease, further investigations are recommended to examine the location and extent of disease in the small bowel, usually including small bowel follow-through or small bowel enema and, less often, abdominal ultrasound, CT and MRI scanning.[6]
-Gastroduodenoscopy and biopsy are only recommended in patients with upper gastrointestinal symptoms.[6]
For perianal disease:
Pelvic MRI should be the initial procedure because it is accurate and non-invasive, although it is not needed routinely in simple fistulae.[7]
Examination under anaesthetic is considered the gold standard but only in the hands of an experienced surgeon. It may permit concomitant surgery.
For known Crohns and wanting to know extent of disease- can do small bowel follow through, upper and lower GI
What are you looking for in FBC: anaemia, haematinics- Vit B12/folate
The diagnosis is confirmed by clinical evaluation and a combination of endoscopic, histological, radiological and biochemical investigations

13. Crohn’s Disease- Management
First presentation (NICE guidelines)
Glucocorticoids
Prednisolone, Methylprednisolone IV hydrocortisone
Budesonide
5-ASA
+/- ADD ON Azathioprine or Mercaptopurine
Biologic: Infliximab and Adalimumab
Offer immunotherapy with a conventional glucocorticosteroid (prednisolone,
methylprednisolone or intravenous hydrocortisone) to induce remission in
people with a first presentation or a single inflammatory exacerbation of
Crohn's disease in a 12-month period.
Manmade glucorticoid- The active ingredient in Budesonide, is released from granules in the ileum of the small intestine and the right (proximal) colon, where the inflammation of Crohn's disease occurs. Budesonide acts directly by contact with the ileum and colon
In people who decline, cannot tolerate or in whom glucocorticosteroid
treatment is contraindicated, consider 5-aminosalicylate (5-ASA) treatment
Consider adding azathioprine or mercaptopurine[9] to a conventional
glucocorticosteroid or budesonide[7] to induce remission of Crohn's disease if:
there are two or more inflammatory exacerbations in a 12-month period, or
the glucocorticosteroid dose cannot be tapered.- Monitor for neutropenia in those
taking azathioprine
Infliximab and adalimumab, within their licensed indications, are recommended
as treatment options for adults with severe active Crohn's disease (see )
whose disease has not responded to conventional therapy (including
immunosuppressive and/or corticosteroid treatments),

14. Crohn’s Disease- Management
Maintaining Remission (NICE guidelines)
Offer Azathioprine or Mercaptopurine as Monotherapy
Methotrixate
Surgery- if limited to distal ileum (weighing out the risk Vs benefits) and for complications...
Do not offer a conventional glucocorticosteroid or budesonide to maintain
remission. Do not offer azathioprine, mercaptopurine or methotrexate as monotherapy in acute exacerbations.

15. Crohn’s Disease- ComplicationsB A C C

16. Case Study 2 32 Male Bloody diarrhoea 4/52
Bilateral lower abdominal cramping
Malaise and weight loss
No associated fever, visual changes, arthralgias, or skin lesions
Previously fit and well contractor
Non-smoker, units/week drinker
FHx: Diabetes Mellitus Type 1

17. Ulcerative Colitis- Definition
Chronic Inflammatory
Bowel Disease
Unknown aetiology
Only Large Colon
Classification:
Distal Disease
More extensive disease
Pancolitis
Ulcerative colitis is an idiopathic inflammatory bowel disease that affects the colonic mucosa and is clinically characterized by diarrhea, abdominal pain and hematochezia. The extent of disease is variable and may involve only the rectum (ulcerative proctitis), the left side of the colon to the splenic flexure, or the entire colon (pancolitis). The severity of the disease may also be quite variable histologically, ranging from minimal to florid ulceration and dysplasia. Carcinoma may develop. The typical histological (microscopic) lesion of ulcerative colitis is the crypt abscess, in which the epithelium of the crypt breaks down and the lumen fills with polymorphonuclear cells. The lamina propria is infiltrated with leukocytes. As the crypts are destroyed, normal mucosal architecture is lost and resultant scarring shortens and can narrow the colon.
Distal disease (left-sided colitis): colitis confined to the rectum (proctitis) or rectum and sigmoid colon (proctosigmoiditis).
More extensive disease includes: left-sided colitis (up to the splenic flexure, 40% of patients), extensive colitis (up to the hepatic flexure) and pancolitis (affecting the whole colon, 20% of patients).
Some patients with pancolitis may have involvement of the terminal ileum due to an incompetent ileocaecal valve.

18. Ulcerative Colitis- Epidemiology
More common than Crohn’s
Incidence: 10 per 100,000
Prevalence 240 per 100,000 in the UK
Age of onset: 2 peaks 1) Y (more common)
2) Y
Male:Female= 1:1
Idiopathic: ?autoimmune condition triggered by colonic bacteria  inflammation
Genetic component: sibling of an individual who has IBD 17-35 x more risk of development
Risk of UC decreased in smokers
1) Ulcerative Colitis; NICE Clinical Guideline (Jun 2013)

19. Ulcerative Colitis- Symptoms
Bloody diarrhoea
Abdominal Pain
Tenesmus
Systemic symptoms: malaise, fever, weightless
What is the character of the pain- severe and colicky

20. Ulcerative Colitis- On examination
Unwell, pale, febrile, dehydrated
Abdo pain and tenderness .. + distension
TOXIC MEGACOLON
Worrying signs: Tachycardia, anaemia and fever
Extra- intestinal disease...

21. Ulcerative Colitis- Extra-intestinal
Aphthous ulcers
Ocular manifestations 5%
Episcleritis
Anterior uveitis
Acute arthropathy affecting the large joints 26%
Sacroiliitis
Ankylosing Spondylitis 3%
Deramatology 19%
Pyoderma gangrenosum
Erythema nodosum
Primary Sclerosing Cholangitis
Approximately 4% of patients will have extra-intestinal disease which may include:

22. Ulcerative Colitis- Investigations
Bloods: FBC, LFTs, U+Es, CRP
Serology- pANCA Vs. ASCA
Stool cultures
Imaging
Abdo x-ray- acute setting
Barium enema- can show mucosal structure
Flexible Sigmoidoscopy and Biopsy- for diagnosis
FBC: anaemia, thrombocytosis--VTE
CRP- sensitive to measure disease activity and monitor progress
Plain abdominal radiographs are a useful adjunct to imaging in cases of ulcerative colitis of acute onset. Because of its ability to depict fine mucosal detail, double-contrast barium enema examination also is a valuable technique for diagnosing ulcerative colitis and Crohn disease, even in patients with early disease.

23. Ulcerative Colitis- Management
Aminosalicylates- in 1977 S Kalsi demonstrated that 5-aminosalicylic acid (5-ASA) and mesalazine was the therapeutic compound in sulfasalazine
Corticosteriods-
Immune supperessive drugs- azathioprine, methotrixate, tacrolimus
Biologic- Infliximab
Treatment of acute UC- NICE
1) mild to moderate first presentation or inflammatory exacerbation of proctitis or proctosigmoiditis:
a) offer a topical aminosalicylate[1] alone (suppository or enema
b) consider adding an oral aminosalicylate[2] to a topical aminosalicylate or
c) consider an oral aminosalicylate[2] alone   2)  mild to moderate first presentation or inflammatory exacerbation of left-sided or extensive ulcerative colitis: a) offer a high induction dose of an oral aminosalicylate b) consider adding a topical aminosalicylate or oral beclometasone dipropionate   3) ACUTE SEVERE COLITIS: Consider adding intravenous ciclosporin[6] to intravenous corticosteroids or consider surgery
for people:
-who have little or no improvement within 72 hours of starting intravenous
corticosteroids or
-whose symptoms worsen at any time despite corticosteroid treatment
a) Topical aminosalicylate alone (suppository or enema
b) ?ADD PO aminosalicylate to a topical aminosalicylate OR
c) consider an PO aminosalicylate alone
a) PO Aminosalicylate - High induction dose of an
b) ?ADD topical Aminosalicylate OR PO beclometasone dipropionate
If no improvement 72 hrs despite IV Hydrocortisone OR
Symptoms worsen to pancolitis:
a) ADD IV Ciclosporin to IV steroids

24. Ulcerative Colitis- Management
Indications for Surgery:
Unresponsive to medical treatment
Significantly affecting quality of life
Growth retardation in Children
Life-threatening complications...
Bleeding
Toxic Megacolon
Impending perforation
Carcinoma

25. Any Questions?

26. SUMMARY

27. Summary: Crohn’s Vs. UC (1)
Symptoms of Crohn's Disease
Abdominal pain, cramping or swelling
Anaemia
Fever
Gastrointestinal bleeding
Joint pain
Malabsorption
Persistent or recurrent diarrhoea
Stomach ulcers
Vomiting
Weight loss
Symptoms of Ulcerative Colitis
Bloody diarrhoea
Abdominal pain or discomfort
Anaemia caused by severe bleeding
Dehydration
Fatigue
Loss of appetite
Rectal bleeding
Urgent bowel movements

28. SUMMARY: Crohn’s Vs. UC (2)

29. SUMMARY- Crohn’s Vs. UC (3)
There are, however, important pathological and clinical differences that distinguish these inflammatory disease processes. Clinically, Crohn’s disease tends to present more frequently with abdominal pain and perianal disease, whereas ulcerative colitis is more often characterized by gastrointestinal bleeding. Cobblestoning mucosa and aphthous or linear ulcers characterize the endoscopic appearance of Crohn’s disease. Ulcerative colitis presents with diffuse continuous involvement of the mucosa. Radiographic studies of patients with Crohn’s disease characteristically show fistulas, asymmetry and ileal involvement. In contrast, radiographic studies of patients with ulcerative colitis show continuous disease without fistulizing or ileal disease (Figure 3).  
Pathologically, Crohn's disease features mucosal discontinuity, transmural involvement and granulomas. In contrast, ulcerative colitis does not. Crypt abscesses and granulomas are present only in Crohn's disease. Figure 4 compares the appearance of the colon, the histology, and endoscopic views of normal, Crohn’s disease, and ulcerative colitis patients.

30. SUMMARY: Crohn’s Vs. UC (2)

31. LEARNING POINTS RELAPSE AND REMITTING MANAGE THE PATIENT
BONE PROTECTION- IF ON LONG-TERM STROIDS
TEST FOR TB BEFORE STARTING INFLIXIMAB
RISK OF COLONIC CARCINIMA IN UC

32. THANK YOU!!