Page created on February 23, 2019. Last updated on September 15, 2021 at 17:14
Inflammatory bowel disease
Introduction and epidemiology
Inflammatory bowel disease (IBD) is an umbrella term for two idiopathic conditions; Crohn disease (CD) and ulcerative colitis (UC). Both are chronic diseases of the gastrointestinal tract that involve some inappropriate immune activation of the mucosa. Luckily for us the two diseases have different features that can be used to differentiate them. We’ll give a summary of the differences at the end of this topic.
IBD is a chronic disease, but it isn’t always active. There are usually periods of active disease with weeks or months of asymptomatic periods between them. The asymptomatic periods are called remission while the symptomatic periods are called flares. Several factors may provoke a flare-up, like stress, specific types of food, or cigarette smoking. However, most flares occur without an apparent trigger.
The disease usually presents during adolescence or in young adults, although there is a second peak of incidence around the age of 50s. It’s most prevalent in Western countries like North America, northern Europe and Australia, and more common in the Northern parts of these regions compared to the Southern parts.
IBD is commonly asked on the exam and repeated numerous times in various later subjects. It’s advantageous to know IBD well.
Several risk factors are known:
- Family history
- Genetic predisposition (NOD2 mutation, HLA-B27
- Diet poor in fibre and rich in total fat and animal fat
- White or Jewish ethnicity
- Absence of breastfeeding
- NSAID use
- Previous GI infection
Interestingly enough, the risk of UC is decreased in people who smoke. The risk for CD is increased however, so don’t start smoking 🚬.
The causes of IBD are not known. We know that there are multiple factors, both genetic and environmental. The pathogenesis involves defects in the mucosal immunity, epithelium, and the intestinal microbiota, leading to chronic inflammation.
One model states that epithelial defects in people with IBD allow bacterial components to transverse the epithelial barrier and enter the mucosa. This activates adaptive and innate immune responses, causing immune cells to release TNF. Here the genetic defects enter the picture, as people with these defects respond to the TNF by further increasing epithelial permeability, allowing even more bacterial components to enter. This is the beginning of a self-amplifying cycle.
Both types of IBD carry the risk for many extraintestinal manifestations of the disease. People with IBD have increased risk for:
- Primary sclerosing cholangitis
- Erythema nodosum
- Pyoderma gangrenosum
- Ankylosing spondylitis
- Aphthous stomatitis
Crohn disease may affect the entire GI tract, from the rectum to the oral cavity. It most frequently affects the terminal ileum and coecum.
In homozygotic twins where one twin has CD the other twin has 50% risk for developing CD as well. This shows that genetics are highly involved in the development of the disease but not the only important factor. The gene NOD2 is especially implicated in CD.
Characteristic for CD is the presence of multiple, separate lesions with sharp border between the diseases part and the healthy colon. This morphology is called skip lesions, as the inflammation appears to “skip” some parts of the mucosa. The lesions are deep and may be transmural. The lesions are depressed compared to the healthy mucosa, which gives the affected area a cobblestone-like appearance.
The lesions in CD begin as aphthous ulcers. These ulcers are deep but narrow, sometimes described as if they were cut by a knife. These ulcers may develop into fissures, deep lesions between mucosal folds that may extend through the whole wall of the intestine, potentially causing perforation.
Due to transmural oedema, inflammation, submucosal fibrosis, and hypertrophy of the muscularis propria may strictures (stenosis, narrowing) develop. These strictures can narrow the lumen, causing bowel obstruction.
In healthy intestine the mesenteric fat is separated from the serosal surface of the intestine. In CD this mesenteric fat slowly extends to and covers the serosal surface. This phenomenon is called creeping fat.
Histologically, infiltration by lymphocytes, plasma cells, eosinophils and neutrophils is typical. In CD the colonic crypts take on weird, branching shapes instead of the normally straight shape. This phenomenon is called cryptal distortion. Cryptitis, where the aforementioned immune cells infiltrate the walls of the colonic crypts can be present. Another sign is cryptal abscess, where the immune cells infiltrate into the lumen of the crypt and not just the wall.
Noncaseating granulomas are found in 35% of CD patients. Paneth cells, the antimicrobial cells in the crypt epithelium, aren’t usually found in the colon. In cases of CD where the colon is affected there can be Paneth cells present due to Paneth cell metaplasia. Pseudopyloric metaplasia, where the intestinal epithelium changes to something more similar to the pyloric epithelium, can also be present.
Because the terminal ileum is commonly affected can the absorption of B12 and intrinsic factor be deficient. Iron deficiency, protein deficiency and generalized nutrient malabsorption may occur. Malabsorption of fatty acids can lead to excess absorption of oxalate, which will be filtered out by the kidney. This increases the risk for calcium oxalate kidney stones.
The previously mentioned strictures may become severe and require surgical resection. Surgical resection of diseased areas isn’t curative as the disease often recurs at the site of anastomosis. Treatment is therefore conservative, usually with immune-supressing drugs which prolong the asymptomatic periods and prevents flare-ups. Antibiotics may be useful.
Fistulas may develop between the bowel and the bladder, vagina or even the skin. Perforations and peritoneal abscesses are common. People who have colonic involvement of Crohn have higher risk for colonic adenocarcinoma, but not as much as in UC.
UC is similar to Crohn disease in some ways but different in many other. The biggest difference perhaps is that UC can only affect the colon, and that the inflammation is never deeper than the submucosa.
UC always starts in the rectum and may spread proximally. If UC only affects the rectum is the condition called ulcerative proctitis, if it affects the whole colon is it called ulcerative pancolitis. If there is pancolitis there may be a small “spill-over” of inflammation into the terminal ileum, a condition called backwash ileitis.
The ulcers in UC are broad with a large diameter, but superficial. Due to regeneration of the ulcers the regenerating mucosa often bulges into the lumen, forming what’s known as pseudopolyps. The ulcers in UC are never transmural; they mostly penetrate the mucosa and submucosa and not deeper.
There is rarely mural thickening due to fibrosis, so strictures rarely occur. However the inflammatory process may damage the muscularis propria and prevent it from functioning properly. This causes the affected bowel to lose its muscular tone, causing it to dilate and becoming toxic megacolon. This has a significant risk of perforation.
The histology of UC is similar to that of CD, except that there are no granulomas in ulcerative colitis.
UC carries a higher risk for colonic adenocarcinoma than CD because it always affects the colon.
Like CD, UC is primarily treated conservatively with immunosuppressant drugs. However, total colectomy will cure UC if conservative treatment is insufficient.
|Feature||Crohn disease||Ulcerative colitits|
|Affected region||Anywhere in GI tract. Commonly terminal ileum||Only colon|
|Inflammation||Transmural||Mucosa and submucosa only|
|Ulcers||Deep, knife-like (aphthous ulcer)||Superficial, broad-based|
|Recurrence after surgery||Yes||No|
7. Diverticulosis of the colon. Pathology of colonic polyps
9. Colorectal malignancies and their relationship to polypous lesions
Theoretical exam topics