From this module you will learn:
- Factors that cause Crohn’s disease
- Symptoms of the condition and how it is diagnosed
- Primary medications used to manage this inflammatory disorder
Download this module - this includes the 5 minute test - here.
Inflammatory bowel disease (IBD) describes both Crohn’s disease and ulcerative colitis (UC). These are relapsing and remitting conditions of the gut – meaning patients have periods where they can be free from symptoms, before falling back into the symptom phase.
The causes of Crohn’s and UC are still unclear, but it is thought that genetic influence, immunology and environmental factors play roles. However, the two conditions are distinct in terms of presentation and treatment. Last week’s module covers UC.
The first description of Crohn’s was made in 1769 by Giovanni Morgagni, an Italian anatomist. But it wasn’t until the 1930s that the disease was formally identified by Burrill Bernard Crohn and his colleagues.
Dr Crohn refused to accept the – at the time – accepted diagnosis of intestinal tuberculosis for the condition. His research led to him, and his colleagues, publishing a landmark paper identifying Crohn’s in 1932.
Since then, there have been many advances in the treatment of Crohn’s, including the first biologic treatment being approved in 1998, and the first identification of a genetic mutation related to Crohn’s in 2001.
Crohn’s is more prevalent in those of white European descent and in urban areas. It is estimated that there are at least 115,000 people in the UK living with Crohn’s.
Causes of Crohn’s
The source of Crohn’s disease is still unclear. However, there is a genetic element, as 15-20% of patients have an affected family member and anyone who has a sibling with Crohn’s is 30 times more likely to develop it.
Environmental factors – such as the use of antibiotics and oral contraceptives, and exposure to certain bacteria – can also influence the likelihood of developing the condition. One theory related to this is the “cold chain hypothesis”, which suggests incidents of Crohn’s have risen along with the use of domestic refrigeration, due to bacteria that thrives in low temperatures.
Smoking increases the risk of having Crohn’s by up to four-fold. The relative risk associated with smoking for women may be greater than for men. Smokers also usually have a more aggressive presentation of the disease.
The sites of Crohn’s have also been linked with the duration of smoking habit and number of cigarettes smoked, suggesting that small bowel and ileocolonic disease – located in the ileum and colon – are more common in heavy smokers.
Signs and symptoms of Crohn’s
Crohn’s can occur in any part of the gut, from the mouth to the anus, but the ileum – the third portion of the small intestine – is a commonly affected area. The inflammation is transmural, meaning it penetrates through all layers of the intestine. It is usually patchy and will vary in size, and there will be sections of the gut which will remain healthy and normal.
Symptoms vary in severity, with a mixture of acute exacerbations and periods of remission, the duration of which can also change.
Common signs and symptoms of Crohn’s are:
abdominal pain and cramping – often on the right hand side after eating.
anal fissure – a tear or an open sore in the anal canal (the section between the rectum and anus) which causes pain and bleeding.
anaemia – due to low iron levels from blood loss from stools and anal fissures.
extreme tiredness or fatigue – caused by the body’s response to Crohn’s, and disturbed sleep caused by pain.
oral inflammation – mouth ulcers, mouth sores and gum inflammation may be accompanied by other symptoms along the alimentary canal.
loss of appetite – can occur as eating may also be associated with nausea, pain, bloating and diarrhoea.
recurrent diarrhoea – may be bloody or contain mucous; often referred to as chronic.
weight loss – this can be related to a loss of appetite, but it may also be due to malabsorption of nutrients or an increase in energy expenditure. Excessive weight can lead to a weakened immune system and poor wound healing.
Further complications and diseases can also manifest, such as: osteoporosis; renal disease; gallstones and renal stones; bowel strictures; anal fistulas (a tunnel that develops between the end of the bowel and the skin near the anus) and perforations (holes in the walls of colon); arthritis (see below); and liver disease.
It is important to exclude other intestinal conditions with similar symptoms, so the right treatment for Crohn’s can be initiated. Symptom history combined with an ileocolonoscopy with a biopsy are used to confirm Crohn’s and its severity.
However, other tests can be useful, so a full blood count, urea and electrolytes, liver function tests, C-reactive protein (CRP), erythrocyte sedimentation rate and stool cultures should also be carried out to confirm a diagnosis.
CRP is produced by the liver whenever a condition causes inflammation. High levels, although nonspecific, usually indicate an active inflammatory disease.
Checking for the presence of faecal calprotectin (a calcium-binding protein) in stools is recommended for a differential diagnosis of irritable bowel syndrome (IBS) and because it correlates with the severity of inflammation in the intestines.
CT scans, MRI scans, barium meals, capsule endoscopy and radionuclide scans may be used to identify acute complications, such as bowel obstructions.
Treatment aims to maintain the patient’s quality of life by either: inducing remission of Crohn’s; reducing symptoms; or preventing its recurrence. However, there is a need to monitor for, and try to prevent, complications such as osteoporosis, colon cancer, renal disease, and iron, folate and vitamin B12 deficiencies.
A multidisciplinary team working with the patient is vital to ensure best outcomes. The updated 2016 National Institute for health and Care Excellence (Nice) guidelines on treating Crohn’s should be consulted for full details.
Alternative treatment strategies
Diet – Adopting elemental or polymeric diets may be used to induce remission, but these are less effective than corticosteroids.
Vedolizumab – This is a humanised IgG1 monoclonal antibody that binds to a membrane inhibitor on a subset of T-helper lymphocytes responsible for triggering inflammation. This stops the lymphocytes from moving to the gastro-intestinal (GI) tract, where they would adhere to the cells and trigger inflammation. This treatment is given by IV-infusion.
Nice’s recent technology appraisal for vedolizumab recommends it as an option in moderate-to-severely active Crohn’s if a TNF-alpha inhibitor has failed, is not tolerated, or is contra-indicated. It must be provided by the manufacturer with a specific discount.
The correct form of medication will help to ensure that the right part of the gut is targeted. For example:
- suppositories – to target the rectum
- enemas – use for the last segment of the colon
- foam – for targeting the sigmoid colon (which connects the colon to the rectum).
Budesonide comes in three forms, with differing release characteristics, which may affect efficacy.
Treatments to maintain remission
Immunosuppressive medications – such as azathioprine or mercaptopurine as a monotherapy – are recommended if the patient has been given glucocorticosteroid or budesonide to induce remission, or during any stage of their treatment if they have not already received an immunosuppressive.
Methotrexate is recommended when azathioprine and mercaptopurine are not suitable due to contraindication or intolerance, or if they were used to induce remission. Corticosteroids or budesonide should not be used to maintain remission.
It is important that patients are not given conventional glucocorticosteroids or budesonide to maintain remission, because of the risk of long-term side effects.
When counselling patients on whether to take medication to maintain remission or not, there is a need balance the risks of relapse against the potential side-effects of medications.
You should reiterate the benefits of not smoking – it greatly reduces the risk of complications, particularly bowel cancer – and ensure the patient knows symptoms that suggest a relapse.
If a relapse does occur, patients should know who to contact, eg their GP or GI specialist. Relapse is common and occurs in around 50% of all patients within the first 12 months of diagnosis.
Additional medical treatment
During the course of Crohn’s, other medication may be required to treat other symptoms, including:
antispasmodics for abdominal cramps, after excluding intestinal obstruction as a cause.
bile acid sequestrants for control of secretory diarrhoea (eg cholestyramine).
loperamide for diarrhoea – this should not be used during active colitis, as it can lead to toxic megacolon (inflammation in the deep layers of the colon that stops it working and widens it, causing a rupture).
metronidazole, ciprofloxacin or surgery to treat fistula.
sulfasalazine and simple analgesics for arthritis (see table).
topical steroids for oral manifestations of the conditions.
More than half of Crohn’s patients will require surgery. It can be considered as a viable alternative to medical treatment early in the disease’s progress, if the inflammation is limited to the distal ileum, but is not curative, so medical management will be required to maintain remission.
Surgical interventions include:
- abscess drainage
- resection of the bowel
- stricture management
- treatment of acute septic complications.
Azathioprine and mercaptopurine can be considered for retaining remission after surgery when there were multiple resections (removal of all or part of the large intestine) or if the patients has had a complicated or debilitating form of the disease (eg an abscess, involvement of adjacent structures, fistulising or penetrating disease).
Aminosaliclytes (eg 5-aminosalicylic acid – 5-ASA) are only recommended for treatment after surgery.
The risk of osteoporosis in those with Crohn’s is high and prevention is key. This includes maintaining dietary calcium intake at recommended levels, not smoking and undertaking weight-bearing exercise. Bisphosphonates may be required to help prevent bone loss.
Iron, folate and vitamin B12 deficiencies are common in people with Crohn’s, so supplements are required. This may change depending on the treatments given (eg vitamin D supplementation when patients are taking corticosteroids).
Due to an increased risk of colon cancer, patients may be offered a following colonoscopy to determine the likelihood of developing this malignancy.
Corticosteroids – eg prednisolone, methylprednisolone or IV hydrocortisone
Prednisolone 40mg daily, reduced by 5mg weekly
Used by itself or with other treatments.
A dose of 9mg daily given for eight weeks, with a reducing dose for the last two weeks
Recommended for disease affecting the ileum or ascending colon. Less effective than corticosteroids, but has fewer side-effects.
Aminosaliclytes – eg 5-aminosalicylic acid (5-ASA)
Mesalazine (unlicensed) comes in three formulations. Dosage is dependent on the formulation used.
Recommended if corticosteroids and budesonide are unsuitable. Mesalazine is less effective at inducing remission, but has fewer side-effects than the former treatments.
A typical adult dose is 2-2.5mg/kg daily
These immunosuppressive treatments are typically given along with a corticosteroid or budesonide. They are not recommended as a monotherapy. Thiopurine methyltransferase (TPMT) activity must be monitored and a reduced dose used if activity is low. TPMT metabolises thiopurine drugs, such as azathioprine, mercaptopurine and thioguanine. Low TPMT activity decreases metabolism of thiopurines, resulting in higher levels of the drugs in the blood. This causes bone marrow toxicity, leading to anaemia, bleeding, leukopenia, myelosuppression and infections.
A typical adult dose is 1-1.5mg/kg daily
25mg intramuscular injection weekly
This is an add-on treatment to corticosteroids or budesonide, if azathioprine or mercaptopurine are not suitable. It is not recommended as a monotherapy.
5mg/kg via IV infusion, followed by another two weeks later
TNF-alpha inhibitors are biological treatments for severe active Crohn’s, which does not respond to the above treatments. They can also be used when a corticosteroid dose cannot be tapered.
Initial dose of 80mg or 160mg, depending on regimen
About 25% of individuals with Crohn’s will develop rheumatoid arthritis. It is believed that the chronic inflammation in the gut can trigger the inflammatory process seen in arthritis, and that both conditions are genetically linked.
You should ensure patients know about this connection and encourage them to speak to their doctor. Many people will focus on their symptoms in Crohn’s, and may think the pain in their joints is merely associated with natural ageing.
The charity Crohn’s and Colitis UK provides information on these conditions, as well as a helpline.
Carrying a Just Can’t Wait Card can help access private toilet facilities that are otherwise inaccessible (eg toilets located in offices or shops used by staff). The card is obtained from the Bladder and Bowel Foundation, which also provides Radar keys used to access public toilets for people with disabilities.
Although Crohn’s disease can have significant effects on the well-being of patients, pharmacists can help reduce the burden of this disease by advising them on how to take control of their condition.
Crohn’s disease CPD
Reflect What factors increase the risk of Crohn’s disease? Which are the first-line drugs for inducing remission? How common are relapses?
Plan This article contains information about the causes, diagnosis and signs and symptoms of Crohn’s. Drug treatments used to induce and maintain remission, additional medical treatments, surgical interventions and complications are also discussed.
Act Find out more about Crohn’s from the Patient website
Read more about the complications of Crohn’s on the crohns.org.uk website here.
Find out more about nutritional therapy in Crohn’s from the crohns.org.uk website at here.
Identify any patients with Crohn’s who might benefit from a patient consultation or a medicines use review
Evaluate Are you now confident in your knowledge of Crohn’s disease? Could you give advice to patients and carers about its management?