Spotlight on inflammatory bowel disease

Dr IS Reynolds and Mr Reza Kalbassi highlight the latest diagnosis and management approaches to Crohn’s disease and ulcerative colitis

Crohn’s disease (CD) and ulcerative colitis (UC) account for the majority of cases of inflammatory bowel disease (IBD), although there are several rarer variants, such as microscopic colitis, diversion colitis, indeterminate colitis and Behçet’s disease. 

UC results in continuous inflammation from the rectum and extends to varying degrees proximally into the colon. It only affects the colon and rectum, although some patients may have backwash ileitis. CD is more widespread and can affect any part of the gastrointestinal tract from the mouth to the anus. The morphologic expression of disease also differs between UC and CD. UC results in inflammation of the mucosa and submucosa only, whereas CD has transmural inflammation.

There are several other important disease characteristics that assist clinicians in differentiating between these two conditions, although it must be stressed that a definitive diagnosis of one condition over the other is often difficult, particularly early on in the disease.

CD often has skip lesions, whereas UC has continuous, diffuse inflammation beginning in the rectum and extending proximally to varying degrees. Strictures can occur in CD but are not characteristic of UC. Endoscopically-marked pseudopolyp formation and the presence of broad-based ulcers is often seen in UC. In comparison, pseudopolyp formation is less common and the ulcers tend to be deep and knife-like in CD. Perianal fistulae and vitamin malabsorption are a feature of CD, but not of UC. There are also histological differences between the two conditions. Lymphoid reaction, fibrosis, serositis and granuloma formation are features in keeping with CD, although a lymphoid reaction can from time-to-time be seen in UC. While granulomas are felt to be an important diagnostic feature of CD, they are only identified in about one-third of cases.

According to the Irish Society for Colitis and Crohn’s Disease, there are about 20,000 people living in Ireland with IBD. Every year, 5.9 cases of CD arise per 100,000 people living in Ireland and the corresponding figure for UC is 14.9 cases per 100,000 of the population. The incidence of these diseases is lower in Asia, Africa and the Middle East, but appears to rise as countries become more industrialised. This rise has been contributed in part to the ‘hygiene hypothesis’, whereby improved food storage conditions results in less contamination and changes in gut microbiome composition. As a result, the mucosal immune responses are not regulated as tightly, resulting in persistent inflammation.

The exact cause of IBD remains uncertain and is an area of ever-increasing research efforts. While many studies have highlighted potential risk factors, such as an increased risk of CD associated with smoking, it is likely that the onset of disease results from a complex interplay of genetic susceptibility, environmental exposures and alterations in the normal gut bacteria. Mucosal immune response and epithelial defects also play a part in IBD. Perhaps one of the most current interesting areas is the research being carried out on the role of the gut microbiome in IBD. There are far more organisms in the GI lumen than there are human cells in our bodies, so it is no surprise that bacteria play an integral part in the development and progression of IBD.

Symptoms

The spectrum of presentations, symptoms and signs is variable. Many people present with non-specific symptoms of fatigue, malaise and vague abdominal discomfort. On the other end of the spectrum are the more severe, emergency presentations with obstruction, abscess formation, perforation, enterocutaneous fistulae, or rarely in UC, a toxic megacolon. More commonly, patients present with varying degrees of abdominal pain, altered bowel habit, particularly diarrhoea, weight loss and bleeding per rectum. Patients may present with some of the extra-intestinal manifestations of IBD, in particular skin, eye and joint problems and in the setting of UC, primary sclerosing cholangitis.

Diagnosis

Patients should have baseline bloods taken, including an FBC, U&E and a CRP. The diagnosis relies on a combination of clinical history and examination, endoscopic, histopathological and radiological findings. Most patients who present to the outpatients clinic will be referred for a colonoscopy, however many patients will also have a gastroscopy at the same time, particularly if their symptoms are vague. Images and biopsies will be taken and some patients may even be started on treatment straight after their scopes, depending on the findings.

If the patient presents acutely or if the findings from their endoscopy have not fully confirmed the diagnosis, then further investigation, such as imaging, will be recommended. This can be in the form of CT of the abdomen and pelvis with the use of contrast imaging or MRI of the small bowel, which is particularly useful in the setting of CD. Sending stool samples for analysis can be helpful; they can be used to look for an infectious cause of the patient’s symptoms and a faecal calprotectin test can be performed, which is used to distinguish between inflammatory and non-inflammatory conditions of the gastrointestinal tract.

Management

One of the greatest developments in patient care is the establishment of IBD multidisciplinary teams (MDTs). These MDTs ensure that all patients have access to a range of specialists, including a gastroenterologist, a surgeon with a special interest in IBD, a pathologist, a radiologist, a specialist IBD nurse and a specialist IBD dietician. These MDTs ensure that a range of specialists review the patient’s history, all the available data for that patient, and formulate the most appropriate management plan before discussion with the patient.

The management of these conditions is becoming more complex — this is predominantly due to the fact that there are so many treatment options available for patients with IBD. Selecting the treatment that best targets your patient’s disease while minimising side-effects is the goal. While it is reasonable for any doctor to commence treatment for very symptomatic patients who are awaiting appointments with a specialist, most people will agree that long-term treatment of this cohort should be overseen by a medical gastroenterologist.

For those not responding to treatment, discussion at the MDT will help determine the most appropriate next step. In order to determine the most appropriate treatment, the clinician must establish the following three things: What is the disease that is being treated? What is the distribution of that disease? And finally, what is the severity of the disease? There are many guidelines available on the management of IBD. For those looking for a simple stepwise approach, we recommend the UK NICE guidelines.

Typically, treatment of IBD is divided into medical management and when necessary, endoscopic, radiological or surgical management. The aims of medical management are, firstly, to induce remission of disease, and then to maintain that remission so that the patient has a good quality of life, is pain-free and has normal or near-normal function of their bowels. There are a wide range of medications available to induce remission in IBD; the choice of medication will typically depend on the type of IBD the patient has, the severity of that disease, if they are already on any treatment at the time of their flare-up, and any previous response or problems with specific medications.

Medications used to induce remission in CD include conventional steroids, budesonide, 5-aminosalicylate (5-ASA), azathioprine, mercaptopurine, methotrexate and in severe cases, the biologic agents. Included in this class is infliximab and adalimumab, although there are many others. Maintaining remission is attempted with drugs such as 5-ASA, azathioprine or one of the biologic agents. Recently, vedolizumab, a humanised, monoclonal antibody that acts against the α4β7 integrin heterodimer has been used in the setting of CD.

Surgery

Despite optical medical management, more than 70 per cent of patients with CD require surgery within 10 years of diagnosis. However, there are some reports that this number may be declining, with one study showing that 60 per cent of CD patients required an operation within 20 years after diagnosis.

While surgery has been shown to provide good symptomatic relief, reoperation rates are 25 per cent and 35 per cent at five and 10 years, respectively. Patients with CD who develop symptomatic strictures have several options, including endoscopic balloon dilatation, stricturoplasty or a resection. Patients with CD with an intra-abdominal abscess on presentation should initially undergo radiological drainage of the abscess. Once the abscess has been dealt with, a decision can be made regarding the next step in their treatment.

Interestingly, there is some recent evidence to suggest that surgery may be considered a reasonable alternative to infliximab in those with isolated disease of their terminal ileum.

UC treatment

The treatment approach is different for patients with UC. Disease localised to the rectum and sigmoid colon, known as proctosigmoiditis, can be treated with a topical medication in the form of an enema. The treatment may consist of a topical steroid or aminosalicylate. For those with disease affecting the colon more extensively or with more severe inflammation, they will often require oral treatment with steroids or aminosalicylates. If the disease fails to respond to initial treatment, then drugs such as ciclosporin or infliximab may be used to try to induce remission. For those in whom remission is induced with medications, then maintenance therapy may consist of either oral or topical treatments. Some patients with severe colitis will not respond to medical management and require surgery.

An in-depth conversation about the procedure, the risk and benefits, the need for a stoma (either temporary or permanent) and the effects on lifestyle, sexual functioning and psychological wellbeing should be had between the surgeon undertaking the procedure and the patient. In the emergency setting, for severe acute colitis that has not responded to maximum medical therapy, a subtotal colectomy with rectal preservation can be performed.

A decision regarding what to do with the rectum can be made at a later date when the patient’s condition has improved. Some patients may choose to undergo an ileal pouch-anal anastomosis (IPAA). This procedure tends to be carried out in three stages, consisting of abdominal colectomy, completion proctectomy with IPAA and loop ileostomy followed by reversal of the loop ileostomy. The first two stages can be combined into a single stage if circumstances permit. There are reports of performing the whole procedure in a single stage, but only in a carefully-selected group of patients. Patients should be carefully counselled regarding the morbidity associated with pouch surgery.

Potential complications include anastomotic leak, pelvic sepsis, small bowel obstruction, sexual dysfunction, incontinence and frequency. A study from the Cleveland Clinic of 1,885 patients has shown that 96 per cent were happy with their results and 98 per cent would recommend the procedure to other patients. Furthermore, continence rates have been shown to be greater than 70 per cent at five years post-surgery.

Follow-up

Follow-up of patients with IBD is important. Firstly, it is crucial to ensure that their disease is under control on their current treatment regimen and issues with treatment are identified and resolved.

Patients should be monitored for potential side-effects of medication. In particular, patients who have required frequent or prolonged courses of steroids should be monitored for the long list of side-effects associated with these drugs, such as the development of osteoporosis. The follow-up appointments also allow the patient’s nutritional status to be assessed. CD can cause deficiencies in vitamins and trace elements that require supplementation and often, repeat visits to the dietician for reminders of the best available dietary strategies prove to be helpful.

One of the most important reasons to follow-up patients with IBD is to arrange for follow-up endoscopy. These tests allow us to directly visualise the mucosa and see what the disease activity is like and to assess the response to treatment. Most importantly, they allow us to look for the most feared complication of chronic IBD, which is the development of cancer.

While there are many figures available on the exact risk of colorectal cancer in patients with IBD, we know that the risk is higher in those with UC compared to those with CD. In those with UC, the risk may be as high as 8 per cent at 20 years after diagnosis. Furthermore, we know that patients with pre-existing IBD tend to develop cancers that are more aggressive in nature. Frequent colonoscopies are important to try and detect abnormal changes in the colon, allowing these areas to be removed before they progress to severe dysplasia and malignancy.

Conclusion

While it is clear that these conditions can be a cause of serious morbidity for patients, there have been some encouraging trends recently. In particular, it appears that rates of surgery are decreasing for patients with CD. The exact reason for this trend is unclear, however it is likely that some of the newer medications are having a positive impact on patients with IBD. Increasing awareness of these conditions and ongoing research efforts should result in further improved outcomes for IBD patients going forward.

References on request