Crohn’s Disease

Crohn’s Disease

·        = Chronic granulomatous inflammation of the gut

Epidemiology

·        Incidence increasing.  Peaks in 2^nd to 3^rd decade

·        1 per 1000 in UK

·        F > M, W > B

Symptoms & Signs:

·        Malaise, weight loss (65 – 75%), failure to thrive, malabsorption

·        Diarrhoea (70 – 90%)

·        Rectal bleeding (45%)

·        Pain (50%, from inflammation, infection, obstruction, colicky from intermittent obstruction of terminal ileum)

·        Perianal disease (50 – 80%)

·        Mild fever (30 – 40%)

·        Anaemia, glossitis (due to malabsorption)

·        Aphthous ulcers in mouth

·        Erythema nodosum (painful red nodular lesions on shins), pyoderma gangrenosum (recurring skin ulcers – 10 cm), clubbing

·        Asymptomatic periods for weeks-months

·        Attacks may be precipitated by emotional/physical stress

·        Risk factors: genetic, smoking, high sugar/low fibre

Aetiology

·        Type 4 immune reaction: trigger unknown. Cause: ?immune hyper-reactivity

·        Proposed agents: viruses, disordered immunologic response to ingested antigen

·        Genetic susceptibility.  10-fold risk in first-degree relatives 

·        Þ Multifactorial ® abnormal regulation of inflammatory mediators

Investigations

·        Bloods: check for anaemia (including anaemia of chronic disease), malabsorption, inflammatory measurements, ­ESR and acute phase proteins

·        Deficiencies: folate, iron, B12, etc, electrolyte abnormalities

·        Culture to exclude infective causes

·        Sigmoidoscopy/colonoscopy + biopsy

·        Upper GI endoscopy

·        Barium contrast of small & large bowel: strictures, fistula, cobblestone appearance, skip lesions etc

Differential

·        Ileal disease: Tb, Lymphoma

·        Colonic disease: colitis (ulcerative, ischaemic, radiation, collagenous), infection (salmonella, shigella, campylobacter), cancer

·        Malabsorption: lactose intolerance, coeliac disease

Pathology

·        Location:

o   75% terminal ileum

o   50% also involves colon

o   25% colon only (predominantly right side)

o   <5% oesophagus, mouth

·        Macroscopic appearance:

o   Skip lesions

o   Transmural inflammation

o   Thickened, inflexible (resembles rubber hose) with narrow lumen

o   Thickened, fibrosed mesentery and enlarged regional lymph nodes

o   Strictures, fistulas, abscesses

o   Mucosa: varying degrees of erythema and oedema.  Cobblestone mucosa

·        Microscopic appearance:

o   Submucosal and subserosal inflammation with only secondary mucosal involvement (ie glands may be straight, unaffected)

o   Aphthoid ulceration of the mucosa

o   Lymphocytic infiltrate, fibrosis

o   Multifocal granulomatous vasculitis 

o   Non-caseating granulomata (only 60%): can have some Langhans/giant cells (horseshoe pattern of nuclei around periphery of a giant cell), but usually granulomas poorly circumscribed

Treatment

·        Aim: suppress activity, restore quality of live, prevent complications 

·        Diet: nutritional supplements. Malnutrition a real risk, ® growth retardation in kids. May need enteral or TPN feeding for „Bowel Rest‟ ® ¯antigen load (controversial) 

·        Corticosteriods e.g. prednisone: symptomatic relief

·        5-aminosalicylic acids e.g. mezalazine 

·        Antibiotics (mainly colonic and perianal disease, ¯antigen load): metronidazole

·        Steroid sparing immunosuppressives: azathioprine 

·        Cholestyramine: absorbs bile (normally absorbed in the terminal ileum) to stop it getting into the large bowel, where it causes irritation 

·        Surgery

·        Monitor: inflammatory markers

Complications

·        Episcleritis (reddened sclera)

·        Stricture, obstruction, fistulas (to bowel, bladder, vagina)

·        Malnutrition

·        Large & small bowel cancer (5% at 10 years – ie small risk – not screened for)

·        Ankylosing Spondylitis

·        Pyoderma gangrenosum

·        Iritis

·        Arthritis

Comparison with Ulcerative Colitis