Page created on September 16, 2021. Last updated on April 20, 2022 at 18:30

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.

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:

• Uveitis
• Primary sclerosing cholangitis
• Arthritis
• Erythema nodosum
• Pyoderma gangrenosum
• Ankylosing spondylitis
• Aphthous stomatitis

Crohn disease

Introduction

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 marker is useful both for excluding the diagnosis (if negative) and for follow-up.

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, glucocorticoids, 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.

For surgical treatment, see the corresponding surgery – traumatology topic.

Ulcerative colitis

Introduction

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.

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.

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, glucocorticoids, 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.

For surgical treatment, see the corresponding surgery – traumatology topic.

Precancerous states of the GI tract

Barrett oesophagus

For introduction, see the corresponding pathology 2 topic.

Barrett oesophagus is asymptomatic and is often discovered when a patient is being evaluated endoscopically for GERD. The diagnosis is based on biopsy and histology.

All patients with Barrett oesophagus should be on PPI.

Barrett oesophagus with high-grade dysplasia is treated with mucosectomy (endoscopic resection) or endoscopic ablation, same as T1A oesophageal cancer. No dysplasia or low-grade dysplasia may be managed either with regular surveillance or endoscopic removal.

Oral leucoplakia and erythroplakia

For introduction, see the corresponding pathology 2 topic.

These precancerous lesions should be surgically removed, or alternatively, regularly surveyed. Avoiding risk factors is important to prevent recurrence or progression.

Familial adenomatous polyposis

For introduction, see the corresponding pathology 2 topic.

As FAP is autosomal dominant, there is often a family history of the disease, but not always. Genetic testing is necessary for the diagnosis, which shows the characteristic germline mutation in APC.

Because FAP is associated with a 100% risk of progression to CRC by the age of 45, surgery is required in all cases. Surgery is performed at age 16 – 20, or at the time of diagnosis if later than this.

The preferred surgical procedure is the same as for UC, is restorative proctocolectomy with ileum pouch and anal anastomosis.

Atrophic gastritis

For introduction, see the corresponding pathology 2 topic. See also topic 57 of internal medicine.

Atrophic gastritis is commonly asymptomatic. Autoimmune metaplastic atrophic gastritis (AMAG) may cause pernicious anaemia. Environmental metaplastic atrophic gastritis (EMAG, H. pylori associated) may cause peptic ulcers.

Treatment involves eradication of H. pylori for EMAG, B12 supplements for AMAG, and possibly regular endoscopic surveillance (although this is controversial).