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 medical students the two diseases have different features that can be used to differentiate them.

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.

Etiology

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 🚬.

Pathomechanism

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.

Extraintestinal manifestations

Both types of IBD carry the risk for many extraintestinal manifestations of the disease. People with IBD have increased risk for:

Crohn disease

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.

Pathology

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 in CD begin as aphthous ulcers. 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.

Noncaseating granulomas are found in 35% of CD patients. Because the terminal ileum is commonly affected, the absorption of B12 and intrinsic factor can 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.

Clinical features

The cardinal symptoms of CD are crampy abdominal pain (usually right lower quadrant), chronic intermittent diarrhoea, fatigue, and weight loss. Diarrhoea may and may not be bloody. Patients may also present with complications such as aphthous stomatitis, perianal fistula, or abscess.

Crohn disease is associated with certain extraintestinal manifestations, although it’s rare that a patient presents with these. These include arthritis, uveitis, ankylosing spondylitis, erythema nodosum, and pyoderma gangrenosum.

Diagnosis and evaluation

Diagnosis of CD is histological, requiring biopsy. The workup of CD involves MR enterography (to visualise the small bowels) and colonoscopy. Biopsies should be taken from any lesions visible, as well as the terminal ileum. If there are oesophageal or gastric symptoms, upper endoscopy should be performed as well. Laboratory tests should check for anaemia and vitamin deficiencies.

Non-infectious intestinal inflammation correlates directly with the amount of calprotectin in the faeces. Measurement of this protein is useful both for excluding the diagnosis (if negative) and for follow-up (to detect flares). CRP and ESR may be elevated in severe cases. Anti-saccharomyces cerevisiae antibodies (ASCA) is specific for Crohn disease and can be used to distinguish it from UC in uncertain cases.

Treatment

Early treatment is necessary to achieve remission and to maintain it, and to prevent complications. Unfortunately, many patients with CD require surgery due to complications in their lifetime.

Many drugs are used in the treatment of CD, including 5-ASA, corticosteroids, immunosuppressants (azathioprine, 6-MP), and biological therapies, like anti-TNF, anti-integrin, and so on. Choice of treatment depends on the severity. 5-ASA is only effective in colonic Crohn disease. Steroids are often used for induction of remission, rather than for maintenance.

In CD, surgery is used in cases where conservative therapy is insufficient. Surgical resection of inflamed bowels is avoided as much as possible, as inflammation will later recur at the area of the anastomosis. Surgery may treat the acute episode, but possible perioperative complications and long-term complications of losing bowel lengths (short bowel syndrome) means that radical resections must be avoided.

Surgery is indicated for the following cases:

Perianal abscess or complicated fistula
Bowel obstruction due to fibrotic strictures
Persistent refractory local acute ileitis

Strictures are treated with stricture plasty.

Perianal fistulas are treated with a clever technique. A seton (a nonabsorbable suture) is guided through the fistula tract and tied together. The seton allows any fluid to drain alongside it, and it prevents the fistula from closing prematurely, potentially forming an abscess. Inflammation close to the anal sphincter may lead to incontinence and is important to avoid.

After some weeks/months, the seton may be removed and the fistula allowed to close, if deemed peaceful. If not, fistulotomy may be necessary.

Ulcerative colitis

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. Because ulcerative colitis only affects the colon, it can be cured by total colectomy.

Pathology

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.

Clinical features

The cardinal symptoms of UC are bloody diarrhoea with or without mucus, abdominal pain, faecal urgency, and tenesmus.

Like CD, UC may cause extraintestinal manifestations.

Diagnosis and evaluation

Colonoscopy with biopsy is essential. The diagnosis of UC is made in the patient with chronic diarrhoea, colitis on biopsy, and when other causes of diarrhoea have been ruled out.

Stool should be tested for bacterial causes of diarrhoea. P-ANCA is positive in UC and negative in CD and so can be used to distinguish the two. Faecal calprotectin is elevated in UC as well.

Treatment

Early treatment is necessary to achieve remission and to maintain it, and to prevent complications. Unfortunately, many patients with UC require surgery due to complications in their lifetime.

Many drugs are used in the treatment of UC, including 5-ASA, corticosteroids, immunosuppressants (azathioprine, 6-MP), and biological therapies, like anti-TNF. Choice of treatment depends on the severity. 5-ASA is very effective for UC. Steroids are often used for induction of remission, rather than for maintenance.

UC carries an elevated risk for CRC. Patients should undergo regular (every 1 – 3 years) colonoscopy to assess for dysplasia and malignancy.

Surgery plays a bigger role in UC than in CD. Total colectomy cures the disease and is therefore a valid option in severe cases.

Surgery is indicated for the following cases:

Refractory disease – where no remission can be achieved, or relapse is frequent
Colonic dysplasia or carcinoma
Severe acute UC (perforation, toxic megacolon)

The preferred surgical procedure for UC is restorative proctocolectomy with ileum pouch and anal anastomosis. This involves resection of the entire colon and rectum, while sparing the anal sphincter. An artificial rectum (the ileum pouch) is created by using loops of ileum to serve as a reservoir for faeces, which is then anastomosed with the anus.

Total colectomy with end ileostomy is a possible alternative.