inflammatory bowel disease dr. wm simmonds internal medicine gastroenterology 29/08/2011
TRANSCRIPT
Inflammatory Bowel Disease
Dr. WM SimmondsInternal MedicineGastroenterology
29/08/2011
Inflammatory Bowel DiseaseObjectives
Understand the pathogenesis of inflammatory bowel disease
Know the differences between Crohn`s disease and ulcerative colitis
Have an approach to the new patient with bloody diarrhoea
Know the differential diagnosis of IBD Know the exta-intestinal manifestations of IBD Know the principles of therapy of inflammatory bowel
disease
Inflammatory Bowel DiseaseIntroduction
Inflammatory bowel disease (IBD) is an immune mediated, heterogeneous syndrome which is divided into 2 major phenotypes:– Crohn`s disease (CD)– Ulcerative Colitis(UC).
There is no pathognomomic test for either CD or UC.
Diagnosis is made on a combination of clinical, radiological, endoscopic and histological grounds.
Inflammatory Bowel DiseaseEpidemiology
IBD is a condition of developed countries and outside of Europe, the United Kingdom and North America, is seen in Australia, South-Africa, and Israel at an appreciable frequency.
IBD is more common in urban areas and in high socioeconomic settings.
It is more common in caucasians, and especially those of Jewish extraction.
It occurs less frequently in other race groups. Smokers have double the risk of developing CD as opposed to non-
smokers. In contrast to this, smoking protects against UC. First degree relatives of those with IBD have an increased risk of
developing IBD.
Inflammatory Bowel DiseaseEtiology and pathogenesis
IBD is currently thought to be due to a dysregulated immune response to an as yet unidentified environmental antigen (possibly enteric microbes).
As such the abnormal immune response develops in those with a genetic predisposition, and is modified by certain factors (smoking).
The current hypothesis holds that the immune response in patients with IBD is against normal bowel flora which is erroneously perceived as being pathogenic.
Inflammatory Bowel DiseaseEtiology and pathogenesis
Numerous genetic polymorphisms have been identified to date which confer a certain risk, and in certain cases predict disease behaviour (e.g. NOD2/CARD15 on chromosome 16, which is associated with CD of the terminal ileum).
Some genetic polymorphisms are specific for CD or UC and some are shared. Genes implicated are involved in regulation of the innate immune system, the adaptive immune system and autophagy.
An alternative hypothesis that patients with IBD have an abnormalities in mucosal defence (defensin production).
Ulcerative Colitis
Disease is confined to the large bowel (that is apart from extra-intestinal manifestations).
The disease is characterised by mucosal inflammation of the large bowel.
Perianal disease, fistulas and small bowel strictures are NOT part of the clinical picture and are suggestive of CD.
Ulcerative ColitisClinical picture
Blood per rectum Bloody diarrhoea (including nocturnally). Blood
macroscopically visible in 95% of active disease. Cramps (especially before bowel movements) Urgency and at times incontinence Tenesmus Tenderness over inflamed colon Extra intestinal manifestations
Ulcerative ColitisEndoscopic characteristics
Rectum almost always involved Extends continuously for varying distances
proximally 20% have pan-colitis Pan-colitics may have “backwash ileitis” Longstanding colitis may manifest as a featureless
colon, which is narrow and shortened Pseudopolyps are a manifestation of prior severe
inflammation
Ulcerative Colitis
Ulcerative Colitis Severity:Truelove en Witts Classification
Mild Severe <4 stools per day >6 liquid stools per day
Minimal or no bleeding Bloody
No fever T >37.5 C⁰ ⁰
No tachycardia Pulse > 90bpm
Mild anaemia at most Hb <10.5(<75%)
ESR <30mm/H ESR >30mm/H
Ulcerative ColitisEndoscopic grading of UC
Mayo grade:1. Loss of vascular pattern
2. Friability
3. Spontaneous haemorrhage
Ulcerative ColitisMicroscopic characteristics
Inflammation is limited to mucosa and superficial sub mucosa, except with fulminant colitis when it may become transmural
Features of chronicity Crypt architectural distortion (branching and fallout) Basal plasma cells and lymphoid aggregates
Active disease Neutrophyl infiltration of epithelium and crypt abscesses
Ulcerative Colitis
Ulcerative ColitisRadiological Characteristics
Plain abdominal x-ray Collapse of involved segment Haustral thickening (“thumb printing”) Dilated colon (>6 cm dilatation of caecum or transverse implies
megacolon)
Ba enema (not used much now) Ulceration Featureless, shortened colon (chronicity features) “lead pipe”
CT scan Dilated loops of colon Enhancement of colonic wall
Ulcerative Colitis
Ulcerative ColitisComplications
Colonic haemorrhage Toxic megacolon Perforation Longstanding disease (> 10 years) increases
the risk of colon Ca.
Crohn’s Disease
Transmural inflammation of bowel, which may affect any part of the GI tract from the mouth to the anus, but tends to affect individual patients in a particular location, which remains stable over time.
It follows that resected Crohn`s disease tends to recur at the site of resection.
Crohn’s Disease
Disease behaviour may follow one of 3 patterns or combinations there of, i.e.– Luminal inflammatory disease– Stricturing disease– Fistulating /penetrating disease.
Crohn’s Disease
Disease pattern/behaviour /ultimate
phenotype may not be apparent
initially and develops over a period
of years.– 30% of patients have isolated ileal disease– 30% have ileo-colitis
– 30% have isolated colitis. Peri-anal disease with
fisures and fistulas is common. Upper gastrointestinal
involvement occurs less frequently.
Crohn’s DiseaseClinical features
Weight loss Diarrhoea (only bloody in 50% of patients with colonic disease) Abdominal pain Symptoms of obstruction (if stricturing disease) Peri-anal symptoms and disease Palpable abdominal mass High fever suggests abscess formation (intra-abdominal,
ischio-rectal) General features of chronic inflammation with pallor, cachexia if
severe uncontrolled disease.
Crohn’s DiseaseEndoscopic characteristics
Depends on distribution Ileitis Colitis
Rectum involved in 50% of patients with colitis Ulceration:
Aphthous Stellate Serpigenous Skip lesions
Crohn’s Disease
Crohn’s DiseaseMicroscopic characteristics
Transmural inflammation Granulomas (non-caseating)
Only seen in 20% of mucosal biopsies and 50% of full thickness biopsies
Crohn’s DiseaseRadiological characteristics
Ba small bowel enemas Strictures (“string sign”) Separation of loops (inflammation with thickening of the bowel wall) Mucosal ulceration Fistulous tracts
CT scan Abscesses/fluid collections Thickened bowel
MRI Especially good for perianal disease Fistulas
Crohn’s Disease
Crohn’s DiseaseComplications
Strictures Fistulas
Entero-enteric Entero-vaginal (usually only after hysterectomy) Entero-cutaneous Recto-vaginal Peri-anal
Abscess formation Gallstones Kidney stones (oxalate)
Extra-intestinal manifestations
Associated with disease activity
Independant of disease activity
ArthropathyPauciarticular (type 1) large peripheral joints
ArthropathySmall joint peripheral arthropathy (type 2)Axial arthropathy (HLA B27)
Sacro-ileitisAnkylosing spondylitis
Ocular manifestations-Episcleritis
Ocular manifestations-Uveitis
Skin-Erythema nodosum
Skin-Pyoderma gangrenosum
Hepato-biliary-PSC
Uveitis
Erythema nodosum
Pyoderma gangrenosum
Differential diagnosis of IBD
Infectious Non-infectious
-Bacteria– Salmonella– Shigella– Campylobacter– Yersinia (Ileitis)– E.coli (enteroadherent, enteroinvasive,
enterohemorrhagic)– Clostridium difficile
-Inflammatory– Diverticular colitis– Ischaemic colitis– Radiation colitis– Solitary rectal ulceration– Appendicitis– Behcet’s disease
-Mycobacateria– Tuberculosis (Ileo-caecal disease)
-Parasites– Entamoeba histolytica– Trichuris trichura (whipwurm)– Necator americanus (hakwurm)– Strongyloides stercoralis
-Neoplastic– Lymphoma (terminale ileum)– Carcinoma
Viruses– CMV– HSV– HIV
-Medication– NSAID’s– Chemotherapy– Bowel preparation
-Fungi– Histoplasmosis (ileitis)
Clinical approach to a patient with bloody diarrhoea
History and clinical examination Stool sample
Microscopy, Culture and sensitivity Clostridium difficile toxin assay
Sigmoidoscopy and biopsy (if biopsy available) Full length colonoscopy in the absence of a
diagnosis and persistent disease or alarm features weight loss anaemia, age >50 years)
Truelove en Witt’s Classification
Mild Severe <4 stools per day >6 liquid stools per day
Minimal or no bleeding Bloody
No fever T >37.5 C⁰ ⁰
No tachycardia Pulse > 90bpm
Mild anaemia at most Hb <10.5(<75%)
ESR <30mm/H ESR >30mm/H
Therapy
Induction of remission with corticosteroids Hydrocortisone 100 mg q 6 hourly IVI for 3 days
– Then: Prednisolone 40 mg per day po 1 week Prednisolone 30 mg per day po 1 week Prednisolone 20 mg per day po 1 month (Initiation of
maintenance therapy) Prednisolone 15 mg per day po 1 week Prednisolone 10 mg per day po 1 week Prednisolone 5 mg per day po 1 week
– Stop.
Therapy
• Maintenance of remission (UC)– Mild to moderate UC
5-ASA preparations– Sulphasalazine– Mesalazine– Balsalazide
– Severe or steroid dependant UC Thiopurines
– Azathioprine 2-2.5 mg per kg per day– 6 mercaptopurine 1-1.5 mg per kg per day
– Steroid refractory UC Cyclosporine Anti-TNFα Colectomy
Therapy
Maintenance of remission (CD)– Crohn`s disease(5 ASA probably does NOT work)– Very mild disease (nothing)– Moderate to severe disease
– Azathioprine or 6 MP– Methotrexate
– Primary prophylaxis– Azathioprine or 6 MP
– Severe disease unresponsive to immunomodulators– Biological agents/antibodies
Infliximab (Anti-TNF) Adalimumab Vedolizumab
– ?“Top down” therapy – Biologic agents first.
General measures
Stop smoking (especially CD patients) Avoid NSAID`s Drug compliance Remember complications of therapy
– Steroids: osteoporosis, diabetes, cataracts, osteonecrosis, Cushingoid habitus, hypertension, mood changes
– 5-ASA: bone marrow suppression (rare), and male infertility– Thiopurines hepatitis, pancreatitis, bone marrow suppression– Methotrexate: teratogenic, liver fibrosis
All drugs may be used in pregnancy & before conception (according to indication) except Methotrexate which is absolutely contraindicated.
If you are a GP, remember initial correct diagnosis and therapy should be followed by timely referral to a specialist.
Indications for surgery
UC– Treatment refractory disease– Toxic megacolon– Colonic haemorrhage– Dysplasia/cancer
CD– Strictures/obstruction– Treatment refractory fistulae– Abscesses– Dysplasia/cancer– Massive haemorrhage(rare)
Thank you