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