Crohn’s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD). Both are characterised by chronic inflammation of the intestine leading to symptoms of diarrhoea, abdominal pain, rectal bleeding, fatigue and sometimes loss of weight. The conditions mainly occur in people between the ages of 20 and 40 but can occur in those much younger or older.
Ulcerative colitis essentially only affects the colon (large intestine) and involves a varying length of the colon. Some patients just have the rectum affected, known as proctitis, which usually presents with rectal bleeding, mucus and an urgency to pass stool. More extensive colitis, involving the left side, most or all of the colon, causes diarrhoea as well as the above symptoms. Crohn’s disease, on the other hand, can affect any part of the gut from the mouth to the anus but most commonly results in inflammation near the junction of the small and large intestine.
The inflammation in Crohn’s disease is more intense with deeper ulceration and can often lead to narrowing of the intestine causing obstruction. Pain is therefore more common with Crohn’s disease as well as the diarrhoea and weight loss.
Despite what you see on line about these conditions, the outlook for patients with Crohn’s disease or ulcerative colitis is excellent, particularly with the increasing number of new treatments available.
Specialist in this area:
Prof Jeremy Sanderson
Dr Jason Dunn
At present it is not known what causes these conditions. CD and UC are similar but are most likely to be two different conditions with different causes. Both have a genetic (familial) tendency with 1 in 5 patients having a relative affected by one of other condition. This genetic tendency may lead to a change in setting of the immune system in the intestine leading to an over-reaction to bacteria or dietary components passing through the gut which then leads to inflammation in the gut lining. Other factors contribute or help to trigger the problem and include smoking, infections and psychological stress. Smoking is interesting in that whilst it clearly worsens CD, it appears to protect against UC. Some drugs may also trigger the inflammation, particularly anti-inflammatory drugs used for arthritis (NSAID’s).
In UC, it seems likely that the mix of bacteria in the colon changes (loss of bacterial diversity in the colonic bacterial flora – the microbiome) and this allows the more proinflammatory bacteria to stimulate an immune response and hence cause inflammation. An alternative theory is that the immune system in the gut is genetically different and overreacts to the normal resident bacteria (it is not clear who throws the first stone so to speak!). However, given the role of the resident gut bacteria in UC, there is interest in how diet, probiotics and other ways of modulating the gut bacteria (including faecal microbiota transplantation) might improve the condition. Whilst drug treatment is important, dietary and lifestyle modification and other measures to target the gut microbiota are a key part of overall treatment.
In CD, however, it seems likely that a more narrow range of bacteria are involved in the altered immune response in the gut that leads to inflammation.
The most frequent test to diagnose IBD is a colonoscopy in which a flexible camera is used to examine the large intestine and last part of the small intestine, usually under moderate sedation. Other tests are used to examine other parts of the intestine depending on the symptoms and include upper GI endoscopy, barium studies, CT and MRI scans and wireless capsule endoscopy (pill camera). Blood tests are used to show levels of inflammation and to monitor the effects of treatment. Stool tests are used to exclude infection and to measure inflammation (faecal calprotectin).
At present, the cause of Crohn's Disease and Ulcerative Colitis is not known. However, as one of the main features is an over-reactive immune system in the intestine, most successful treatments are aimed at damping this down. In UC, but also in CD, this can often involve simple medicines, e.g. Mesalazine, which reduce inflammation within the gut wall and are only minimally absorbed into the body. These can be given as oral medicine or, when the inflammation is in the rectum or last part of the colon, suppositories or enemas can deliver the medicine more effectively.
As discussed above, there is increasing interest in targeting the bacterial flora in the intestine. Antibiotics can certainly be effective in a flare-up of CD, or where there is a definite infection. Probiotics (there is good evidence for benefit from certain stronger ones so these should be discussed with the specialist) may be of benefit, especially in UC.
When the symptoms and inflammation in the gut are more severe, stronger medicines are needed. These include steroids which are the usual first choice medicine for reducing severe symptoms and inflammation quickly. Steroids have significant side effects particularly if used long term and are therefore only used as short courses. Newer steroids can target the gut alone without significant absorption (Budesonide, Beclomethasone) and are therefore useful to limit side effects. In UC, this is usually enough to return the condition to a level where mesalazine will help keep the condition in remission. In CD, however, stronger treatment is needed more often. This takes the form of immunosuppressive drugs such as azathioprine, mercaptopurine and methotrexate.
To many patients, the thought of suppressing the immune system does not sound very good when first mentioned as a treatment option. However, CD and UC, as above, are conditions in which the immune system in the gut is over-active, and suppressing this makes perfect sense as a logical treatment approach. Also, the level of immunosuppression induced by drugs (azathioprine, mercaptopurine, methotrexate and others) is not actually that significant. The risk of getting infections, for example, is only increased a little. The drugs do need to be monitored to make sure the immune system is not over suppressed and therefore regular blood tests are needed. Blood tests before starting can also identify certain people who should only have reduced doses of azathioprine (TPMT testing). A lot more is now known about how to tailor the dose of these drugs to individuals (a particular area of expertise of Professor Sanderson) and hence reduce the risks but maximise the benefits.
Importantly, immunosuppressive drugs are effective in inducing and maintaining remission and helping to come off or avoid steroids. Used properly, they are an essential part of the successful treatment of CD and UC (especially CD).
These have been available for many years now and form an important part of the management of more severe CD and refractory UC. The treatments involve infusions or injections of antibodies which target TNF, one of the main mediators of the inflammation in CD and UC, of other key molecules controlling the inflammatory response in the intestine. These treatments can be very effective but can also cause side effects such as infection or allergic reactions. They are reserved for more severe cases where the balance of risk versus benefit falls strongly in favour of benefit. It is true to say that these drugs have made a huge difference to the outcome of more severe CD and UC with reduced complications, reduced need for operations and an improved prognosis and quality of life. As a result, there is a move towards earlier use particularly where we can predict a patient likely to have a more severe pattern of disease over time. This is a frequent discussion point between patient and specialist. Patients and their relatives often fear the risks of going on to the stronger medication – in fact, the bigger fear is the risks of the condition not being fully treated and interfering with quality of life, school, university, employment, travel etc……..which are all put back on track by effective treatment.
There is a clear role for bacteria in the cause of CD and UC. In UC, as discussed above, approaches to change the overall diversity of the gut bacteria are the current approach used to augment the response to medical therapy, either through diet or with probiotics. Faecal microbiota transplantation (FMT) remains under evaluation but may well prove to be successful as we learn more about how to tailor this to certain conditions. It is only available in certain centres or as part of clinical trials.
In CD, however, it is likely that a narrower range of bacteria are involved. This might include strains of E.coli that get into the bowel wall or, for example, Listeria. Mycobacterium paratuberculosis (MAP) is a species of mycobacteria from the same family of bacteria that causes Tuberculosis. It is generally an environmental bacteria but can cause disease in animals, particularly cattle and sheep (Johne’s disease) which is remarkably similar to CD. For years, scientists have been attempting to prove or disprove whether MAP is involved in CD. It is certainly present in the gut wall in patients with the condition (mainly by DNA testing) and rarely present in the gut of those without CD. However, the question remains as to whether it is causing the chronic inflammation or an innocent bystander. Further studies will hopefully resolve this over the next 5 years.
At present, treatment with combinations of antibiotics aimed at killing MAP (ant-MAP antibiotic therapy or AMAT) is an option for treating CD in certain individuals, particularly those in whom we would wish to avoid immunosuppression or biologics for various reasons. AMAT involves taking 2-4 antibiotics (classically Rifabutin, Clarithromycin and Clofazamine, but can also involve Rifampicin, Azithromycin and Ethambutol) for an initial trial period of 3-4 months. If there is genuine evidence of response, then the treatment might be continued for 2 years with appropriate monitoring.
An alternative strategy for the future might be a therapeutic vaccine (MAP vaccine) being generated at Kings College London and at the Jenner Institute in Oxford. A phase 1 clinical trial in patients not taking immunosuppressant therapy is envisaged to start at Guy’s & St. Thomas’ Hospitals, London, in the near future (2019). Professor Jeremy Sanderson can be contacted about this study through the London Digestion office.
Operations (surgery) is a vital part of successful treatment of CD and UC. Up to half of people with CD will need an operation at some stage because of the tendency of segments of the intestine affected by the condition to become narrowed by scar tissue. This causes a blockage in the intestine for which surgery is usually the only effective treatment. In UC, surgery is needed less often but in some cases, the inflammation is so severe, and life threatening, that the colon has to be removed. This can also happen when UC does not respond well to medicines over many years and a patient’s quality of life would be hugely improved by removing the colon (which is effectively a cure for UC as it only affects the colon).
Many people worry about surgery meaning they will have a stoma bag. This is, in fact, rare nowadays. Many people need a stoma bag temporarily (for several months for example) in the recovery phase from delicate surgery but permanent stoma bags are fortunately now needed very rarely.
It is important to view surgery in its proper place – it is not usually a last ditch option – rather it is an important part of the treatment of CD and UC along with other treatments. Done at the right time, it can be one of the best means of getting a patient’s life back on track.
Overall, the prognosis in Crohn's Disease and Ulcerative Colitis is very good and getting better. Whilst the condition is causing problems, work or school is obviously affected and a normal life is difficult. However, most of the time people are well and it is said the average is to have a flare up every 2 years or so. Life expectancy is close to normal.
Crohn’s and Colitis UK offer an excellent support service and can be contacted on www.crohnsandcolitis.org.uk or phone 03002225700. Good information is available on all the various issues facing patients with a diagnosis of CD or UC, including risks and benefits of treatments.
Professor Jeremy Sanderson
Has a specific interest and expertise in the management of CD and UC and receives many referrals for opinions on patients. His approach has always been to consider any option and to try and get every patient’s life back on track in the way they would have liked. Many people have misconceptions about the disease and its treatment and it is often by resolving these that a successful outcome is achieved in a way that restores hope and confidence to a patient.
Dr Jason Dunn
Dr Phil Berry