Crohn's disease Flashcards
Summarise Crohn’s disease
Common presenting symptoms include chronic diarrhoea, weight loss, and right lower quadrant abdominal pain mimicking acute appendicitis.
Diagnosis confirmed by colonoscopy with ileoscopy and tissue biopsy.
Specialist input is required from the time of diagnosis, as treatment regimens require frequent monitoring of clinical response, knowledge of common side effects, and expertise in managing potential serious adverse events.
The overall treatment goals are to induce and maintain remission plus prevent relapse or recurrence.
Complications include extra-intestinal involvement, intestinal obstruction, abscess formation, sinuses, and fistulae.
Define Crohn’s disease
Crohn’s disease (CD) is a disorder of unknown aetiology characterised by transmural inflammation of the gastrointestinal (GI) tract. CD may involve any or all parts of the entire GI tract from mouth to perianal area, although it is usually seen in the terminal ileal and perianal locations. Unlike ulcerative colitis (UC), CD is characterised by skip lesions (where normal bowel mucosa is found between diseased areas). The transmural inflammation often leads to fibrosis causing intestinal obstruction. The inflammation can also result in sinus tracts that burrow through and penetrate the serosa, thereafter giving rise to perforations and fistulae.
Describe the epidemiology of Crohn’s disease
The prevalence of inflammatory bowel disease in North America is in excess of 0.3%.[8] It is estimated that there are around 3 million adults affected with inflammatory bowel disease (either CD or ulcerative colitis [UC]) in the US.[9]
A European Commission-funded study of 20 European centres showed that the overall incidence per 100,000 at ages 15 to 64 years (standardised for age and sex) of CD was 5.6. Rates of CD in northern centres were 80% higher than those in the south (rate ratio [RR] = 1.8). For CD the highest reported incidence was in Maastricht (the Netherlands; 9.2) and Amiens (north-west France; 9.2). The lowest incidence of CD was in Ioannina (north-west Greece; 0.9).[10]
The highest incidence of CD is in northern climates and in developed countries, and the lowest in southern climates and less developed areas. The incidence and prevalence seem to be lower in Asia, Japan, and South America. A rise in the incidence of CD has been consistently observed over the last 60 years, although it is now stabilising in Western countries.[8][11] The incidence is now approximately equivalent to that of UC in North America and Europe.[1][12]
The peak age of onset is between 15 and 40 years, and there is a smaller second peak between 60 and 80 years. CD is equally prevalent among men and women. It is more common in white people and Ashkenazi Jews. Some studies have shown a higher prevalence among smokers
Describe the genetic factors involved in the aetiology of Crohn’s
The aetiology of CD remains unclear, with various studies suggesting a role for genetic and environmental factors.
- Genetic factors[14]
Genome-wide association studies have identified over 71 different genetic susceptibility loci, with the strongest associations being between CARD15 (caspase recruitment domain family, member 15), which encodes the NOD2 (nucleotide-binding oligomerisation domain containing 2) pathogen recognition protein, and other loci, such as the IBD5 locus, the autophagy gene ATG16L1 (ATG16 autophagy 16-like 1), and the interleukin-23 receptor.[15][16][17] Genotype may also influence the distribution of CD.[18]
However, research suggests that vital genetic clues have been missed, with all the genes identified to date accounting for <20% of the total heritable risk for CD. This is supported by the fact that the disease-associated loci appear to have a low penetrance and a relatively high frequency in the general population
Describe the environmental factors involved in the aetiology of Crohn’s
. Environmental factors
Include: smoking, oral contraceptive pill, diet high in refined sugar, nutritional deficiencies (especially zinc), and infectious agents (measles virus, and a possible association with Mycobacterium avium paratuberculosis).[20][21][22][23]
Some studies have indicated a possible role of non-steroidal anti-inflammatory drugs in the development of CD.[24][25]
Correlation between acute gastroenteritis and subsequent risk of CD has also been suggested
Describe the pathophysiology of Crohn’s
Current theories about the pathophysiology of CD indicate a role for infectious, immunological, environmental, dietary, and psychosocial factors in a genetically and immunologically susceptible person.[14][20][21][26][27][28]
The initial lesion starts as an inflammatory infiltrate around intestinal crypts that subsequently develops into ulceration of the superficial mucosa. The inflammation progresses to involve deeper layers and forms non-caseating granulomas. These granulomas involve all layers of the intestinal wall and the mesentery and regional lymph nodes. The finding of these granulomas is highly suggestive of CD, yet their absence does not exclude the diagnosis.[29][30]
Early endoscopic findings include hyperaemia and oedema of the inflamed mucosa. This progresses to discrete deep ulcers located transversely and longitudinally, creating a cobblestone appearance. These lesions are separated by healthy areas known as skip lesions
Describe the difference between acute and chronic transmural inflammation
Acute transmural inflammation results in bowel obstruction due to mucosal oedema associated with spasm. Chronic transmural inflammation thickens the bowel wall and leads to scarring, luminal narrowing, and stricture formation. This may lead to fistulisation, sinus tract formation, perforation, and/or abscess formation. Chronic inflammation also damages the intestinal mucosa, resulting in deficient absorptive ability. This can lead to malnutrition, dehydration, and vitamin and nutrient deficiencies. Involvement of the terminal ileum interferes with bile acid absorption, which leads to steatorrhoea, fat-soluble vitamin deficiency, and gallstone formation.[31] Excessive fat in the stool binds to calcium, thereby increasing oxalate absorption and predisposing to oxalate kidney stone formation
Describe the extra-intestinal manifestations of Crohn’s
In addition to manifestations related to the gastrointestinal tract, CD may involve multiple extra-intestinal organs and systems including skin, joints, mouth, eyes, liver, and bile ducts. Some of these disorders have autoimmune mechanisms
Describe the Vienna classification of CD
Vienna classification of CD[3]
Classifies patients with CD into 24 subgroups. Mostly used for research purposes.
Age at diagnosis - when first definitively established by radiology, endoscopy, pathology, or surgery.
A1 <40 years of age.
A2 40 years of age or more.
Location - maximum extent of disease involvement at any time before the first resection. Minimum involvement for a location is aphthous lesion or ulceration. Both small- and large-bowel examination are required for classification.
L1 - terminal ileum - limited to terminal ileum, with or without spill-over into the caecum.
L2 - colon - any colonic location between the caecum and rectum, with no small bowel or upper gastrointestinal involvement.
L3 - ileocolonic - disease of ileum and any location between the ascending colon and rectum.
L4 - upper gastrointestinal - any disease proximal to the terminal ileum (excluding mouth), regardless of additional involvement of the terminal ileum or colon.
Behaviour
B1 - non-stricturing, non-penetrating.
B2 - stricturing - constant luminal narrowing demonstrated by radiological, endoscopic, or surgical-pathological methods, with pre-stenotic dilation or obstructive signs/symptoms, without the presence of penetrating disease, at any time in the course of the disease.
B3 - penetrating - occurrence of intra-abdominal or perianal fistulae, inflammatory masses, and/or abscesses at any time in the course of the disease. Perianal ulcers are included. Postoperative intra-abdominal complications and skin tags are excluded.
Describe a typical case history for CD
A 25-year-old white man presents to his general practitioner with cramping abdominal pain for 2 days. He reports having loose stools and losing 6.8 kg over a 3-month duration. He also reports increased fatigue. On physical examination, his temperature is 37.6°C (99.6°F). Other vital signs are within normal limits. Abdomen is soft with normal bowel sounds and moderate tenderness in the right lower quadrant, without guarding or rigidity. Rectal examination is normal and the stool is guaiac positive. The rest of the examination is unremarkable.
Describe a second typical case history for CD
A 16-year-old girl presents to emergency care with perianal pain and discharge. She reports a 2-year history of intermittent bloody diarrhoea with nocturnal symptoms. On examination, she is apyrexial with normal vital signs. Her abdomen is soft and slightly tender on palpation in the left lower quadrant. Rectal examination is difficult to perform due to pain, but an area of erythematous swelling is visible close to the anal margin, discharging watery pus from its apex. Several anal tags are also present.
Describe some other presentations of CD
Atypical presentations depend on sites of inflammation and extra-intestinal manifestations: musculoskeletal (arthritis, polymyositis); skin (fissures, fistulae, erythema nodosum, pyoderma gangrenosum, ‘metastatic CD’); hepatobiliary (primary sclerosing cholangitis [PSC], bile duct carcinoma, autoimmune hepatitis, pericholangitis, gallstones); pancreatic (acute pancreatitis); ocular (uveitis, episcleritis, scleromalacia, corneal ulcers, retinal vascular disease); blood (anaemia, thrombocythaemia secondary to inflammation, thrombocytopenic purpura); renal (urinary calculi, amyloidosis); neurological (peripheral neuropathy, myelopathy, myasthenia gravis); bronchopulmonary (pulmonary fibrosis, bronchitis, laryngotracheitis); cardiac (pericarditis, myocarditis); hypercoagulability (thrombophlebitis, thromboembolism, vasculitis); thyroid (Hashimoto’s thyroiditis)
